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PubMed2004

An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese.

Association studies were performed to confirm the effect of polymorphisms in apolipoprotein A1 ( ApoA1) on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI). A sequence analysis identified nine polymorphisms in ApoA1. After considering linkage disequilibrium, four polymorphisms in ApoA1 and four polymorphisms in the 5'-flanking regions and 3'-flanking regions from the JSNP database were determined in 1,880 subjects recruited from the Suita study, which represents the general population in Japan. Of the eight polymorphisms tested, the ApoA1 T84C polymorphism had the greatest effect on the levels of HDL-C ( P=0.0005, P(c)=0.0040 corrected by the Bonferroni method) and triglyceride ( P<0.0001, P(c)=0.0008). The ApoA1 MspI polymorphism was not associated with HDL-C or triglyceride levels. We confirmed that the ApoA1 T84C polymorphism was associated with the HDL-C level but not the triglyceride level in patients with MI ( n=637). Moreover, this polymorphism was associated with the incidence of MI in male subjects ( P=0.0326). A logistic analysis indicated that the frequency of MI in the CC genotype was lower than that in the CT+TT genotype ( P=0.0145, OR=0.4955, 95% CI: 0.2746-0.8525). The ApoA1 T84C polymorphism is an important marker for the HDL-C level and may be a new risk marker for MI in Japanese.

Aged↗

PubMed2006

Polymorphisms of the DNA polymerase beta gene in breast cancer.

DNA polymerase beta (Polbeta) provides most of the gap-filling synthesis at apurinic/apyrimidine sites of damaged DNA in the base excision repair pathway. Mutations in the gene encoding DNA polbeta have been identified in various carcinomas. We performed a case-control study to test the association between two polymorphisms in the polbeta gene: a Pro --> Arg change at codon 242 (the Pro242Arg polymorphism) and a Lys --> Met change at codon 289 (the Lys289Met polymorphism) and breast cancer risk and cancer progression. Genotypes were determined in DNA from peripheral blood lymphocytes of 150 breast cancer patients and 150 cancer-free, age-matched women (controls) by PCR-RFLP. A strong association between breast cancer occurrence and the Met/Met phenotype of the Lys289Met polymorphism [odds ratio (OR) 3.67; 95% confidence interval (CI) 1.87-7.56] and the Pro/Arg phenotype of the Pro242Lys polymorphism (OR 1.96; 95% CI 1.15-3.34) was found. Polymorphism-polymorphism interaction between the Met/Met phenotype of the Lys289Met and the Pro/Arg phenotype of the Pro242Arg variants increased the risk of breast cancer (OR 3.05; 95% CI 1.31-7.09). We did not observe any correlation between studied polymorphisms and breast cancer progression evaluated by node-metastasis, tumor size and Bloom-Richardson grading. In conclusion, Polbeta may play a role in the breast carcinogenesis and the Lys289Met polymorphism of the polbeta gene may be considered as an independent, early, molecular diagnostic marker in breast cancer. The Pro242Arg polymorphism may contribute to the carcinogenesis through the interaction with the Lys289Met and therefore may be regarded as a dependent, auxiliary marker.

Breast Neoplasms↗

PubMed1990

Human DNA polymorphisms and methods of analysis.

The current predominant method of analyzing base substitution polymorphisms, RFLP analysis, is likely to be gradually supplanted by methods based on PCR because of the improved sensitivity and genotyping rate. The most promising PCR methods for analysis appear to be allele-specific PCR and single-stranded conformational analysis. The single-stranded conformation approach has already been applied to the scanning of cystic fibrosis exons for new mutations. Linkage mapping projects that cover large segments of the human genome will probably rely, in the coming years, primarily on tandem repeat polymorphisms, particularly microsatellite polymorphisms. Microsatellite polymorphisms have at least a fourfold advantage over base substitution RFLPs because they are twice as informative and can be typed at at least twice the rate. The facioscapulohumeral muscular dystrophy gene was recently mapped in just 6 weeks using microsatellite polymorphisms. Because of the informativeness handicap, it will be difficult for base substitution polymorphisms to overtake tandem repeat markers for large-scale linkage mapping. Methods that allow base substitution polymorphisms to be typed at two or three times the rate of microsatellite markers would have to be developed. Most of the other applications of DNA polymorphisms described in the introduction are also increasingly likely to rely on highly informative tandem repeat markers in the future. Methods for analysis will probably be based on PCR. It is easy to envisage, for example, an automated method for large-scale DNA fingerprinting of individuals based upon a standard set of highly informative, dependable microsatellite polymorphisms. Methods for analyzing base substitution polymorphisms will continue to be important for the diagnostic detection of disease-gene alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗

PubMed2006

PPAR-gamma2 Pro12Ala polymorphism is associated with weight gain in women with gestational diabetes mellitus.

OBJECTIVE: The polymorphisms of peroxisome proliferator-activator receptor-gamma2 (PPAR-gamma2) have been suggested to affect glucose metabolism and weight gain. Both conditions show great variations during pregnancy that makes pregnancy a suitable condition to detect any metabolic abnormalities related to PPAR-gamma2 polymorphisms. The objective of this study is to investigate the prevalence and metabolic impacts of PPAR-gamma2 polymorphism in control pregnant women and in patients with gestational diabetes mellitus (GDM). METHODS: In this case-control study, anthropometric and metabolic variables of 100 non-diabetic pregnant women and of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test (OGTT) were compared on the basis of PPAR-gamma2 polymorphism by univariate analysis of covariance. RESULTS: There were no statistically significant differences in baseline characteristics and the mean 50 g glucose challenge test values of pregnant women in both groups on the basis of PPAR-gamma2 genotype, although patients with Pro12Ala polymorphism were significantly taller in GDM group. The Pro12Ala polymorphism had no effect on 100 g OGTT results of patients with GDM. However, patients with GDM who had Pro12Ala polymorphism gained significantly more weight during their pregnancy. CONCLUSION: The PPAR-gamma2 Pro12Ala polymorphism was observed to have no effect on glucose metabolism in normal pregnant women and women with GDM. However, only the patients with GDM who had this polymorphism gained significantly more weight during their pregnancy. It seems that Pro12Ala polymorphism plays a dynamic and interactive role in the regulation of BMI and glucose homeostasis.

Adult↗

PubMed2004

Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study.

OBJECTIVE: Carriage of thrombophilic and vasoactive polymorphic alleles has been associated with various pregnancy complications. The effect of carrying multiple polymorphisms is not known. We conducted a case-control study to determine the association between eight polymorphisms of thrombophilic and vasoactive genes and the risk of severe preeclampsia. METHODS: The following polymorphisms were analyzed by sequencing-on-chip-technology using solid-phase polymerase chain reaction on oligonucleotide microarrays: factor 5 (F5) Leiden, factor 2 (F2)-prothrombin G20210A, plasminogen activator inhibitor (PAI)-1 4G/5G, nitric oxide synthase (NOS) 3 T768C, NOS 3 Glu298Asp, angiotensinogen (AGT) Met235Thr, estrogen receptor (ER) alpha Pvu II, and mineralcorticoid receptor (MLR) Ser810Leu. The study comprised 24 patients with severe preeclampsia and 24 controls from a cohort of consecutive white women treated at the Obstetrics Department of the University of Vienna Medical School. Genotypes were correlated with clinical data. RESULTS: The investigated polymorphisms did not influence the risk of severe preeclampsia independently. When separately considering the simultaneous carriage of multiple thrombophilic or vasoactive polymorphisms, neither the combined carriage of thrombophilic polymorphisms (F5 Leiden, F2 G20210A, PAI-1 4G/5G), nor the combined carriage of vasoactive polymorphisms (NOS 3 T768C, NOS 3 Glu298Asp, AGT Met235Thr) conferred an increased risk of severe preeclampsia. Cumulative genotype frequencies for at least two homozygous mutant genotypes, however, were nine of 24 (38%) and two of 24 (8%) for the study and control groups, respectively (P <.05). All of these nine women with severe preeclampsia had at least two homozygous mutant genotypes of four polymorphisms, ie, F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, or ER alpha Pvu II. CONCLUSION: Our data fail to document an independent significant influence of the investigated polymorphisms on the risk of severe preeclampsia. In an attempt to build a multigenetic model of severe preeclampsia, the combination of F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, and ER alpha Pvu II was the most effective combination to predict the presence of severe preeclampsia in this small series of white women.

Adult↗

PubMed2006

Association of TNFSF11 gene promoter polymorphisms with bone mineral density in postmenopausal women.

OBJECTIVES: The receptor activator of nuclear factor-kappaB ligand (RANKL) is recognized as one of the important regulators of osteoclastogenesis. The expression of the tumour necrosis factor superfamily, member 11 (TNFSF11) gene, which encodes for RANKL protein, is increased relative to the expression of osteoprotegrin in cases of senile osteoporosis with hip bone fracture. Our aim was to find polymorphisms in the TNFSF11 gene promoter and to investigate their possible association with bone mineral density (BMD). METHODS: The TNFSF11 gene promoter region was screened for the presence of new sequence variations by direct sequencing. DNA sequencing revealed the presence of four sequence variations: -290C>T, -643C>T, -693G>C and -1594G>A. Association of the discovered polymorphisms with BMD was investigated in 115 Slovenian postmenopausal women, using restriction fragment length polymorphism analysis. After a year, bone loss in the association with the identified sequence variations was evaluated in 43 postmenopausal women. RESULTS: Three of the discovered sequence variations (-290C>T, -643C>T, -693G>C) proved to be polymorphic, whereas variation -1594G>A was only found in one patient. The frequencies of genotypes were as follows: CC (27.8%), CT (43.5%), TT (28.7%) for -290C>T polymorphism; CC (23.5%), CT (47.8%), TT (28.7%) for -643C>T polymorphism; and GG (22.6%), GC (51.3%), CC (26.1%) for -693G>C polymorphism. A statistically significant association of genotype with BMD at the femoral neck was observed only in the -290C>T polymorphism. Genotype CC was associated with lower BMD than the TT genotype (P = 0.022). In polymorphism -693G>C, a significant difference in bone loss rate was observed in total hip (P = 0.011) and femoral neck BMD (P = 0.037). CONCLUSIONS: Four sequence variations were identified in the studied region of TNFSF11 gene promoter. Our results of preliminary clinical evaluation suggest that the -290C>T polymorphism in the TNFSF11 gene promoter could contribute to the genetic regulation of BMD.

Aged↗

PubMed2005

Met72Thr polymorphism of pigment epithelium-derived factor gene and susceptibility to age-related macular degeneration.

Age-related macular degeneration (ARMD) is the most common cause of acquired blindness among the people of occupational age. Although the pathogenesis of ARMD is not fully understood, several studies suggest a possible contribution of a genetic factor in the development and progression of ARMD. Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from the conditioned media of human retinal pigment epithelial cells as a factor with potent neuronal differentiating activity in human retinoblastoma cells. Recently, PEDF has been shown to be a highly effective inhibitor of angiogenesis in cell culture and animal models. In addition, PEDF has been found in the vitreous, and its levels were decreased in angiogenic eye diseases, thus suggesting that a loss of PEDF in the eye is functionally important in the pathogenesis of ARMD. A functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) at codon 72 in exon 3 (T/C polymorphism) of the PEDF gene, that results in the formation of BsstSI restriction site, has recently been identified. Since it is well known that a single nucleotide polymorphism and resultant amino acid change often alters the activity or expression level of the target protein, we would like to propose here a novel hypothesis that the Met72Thr polymorphism (T/C polymorphism) of PEDF gene may be a genetic marker for ARMD. Are genotype and allele frequencies of the Met72Thr polymorphism (T/C polymorphism) different between the patients with or without ARMD? Is this polymorphism associated with disease severity and progression? If the answer is yes, does this Met72Thr polymorphism regulate the vitreous levels of PEDF? These clinical studies could provide us with information whether this genetic variant of the PEDF gene could present an attractive candidate susceptibility gene for ARMD.

Amino Acid Substitution↗

PubMed2006

Lack of significant association between -1021C-->T polymorphism in the dopamine beta hydroxylase gene and attention deficit hyperactivity disorder.

Recent trends in medications for attention deficit hyperactivity disorder (ADHD) suggest that norepinephrine (NE) deficiency may contribute to the disease etiology. Dopamine beta hydroxylase (DBH) is the key enzyme which converts dopamine to NE and since DBH gene is considered a major quantitative trait locus for plasma DBH activity, genetic polymorphism may lead to altered NE neurotransmission. Several polymorphisms including a 5' flanking -1021C-->T polymorphism, was reported to be associated with changed DBH activity and an association between -1021C-->T polymorphism with ADHD was observed in Han Chinese children. We have carried out family-based studies with three polymorphisms in the DBH gene, -1021C-->T polymorphism, exon 2*444g/a and intron 5 TaqI RFLP, to explore their association with Indian ADHD cases. Allele and genotype frequency of these polymorphisms in ADHD cases were compared with that of their parents and a control group. Haplotypes obtained were analyzed for linkage disequilibrium (LD). Haplotype-based haplotype relative risk analysis and transmission disequilibrium test showed lack of significant association between transmission of the polymorphisms and ADHD. A haplotype comprising of allele 1 of all polymorphisms showed a slight positive trend towards transmission from parents to ADHD probands. Strong LD was observed between *444g/a and TaqI RFLP in all the groups. However, low D' values and corresponding log of odds scores in the control group as compared to the ADHD families indicated that, the incidence of the two polymorphisms being transmitted together could be higher in ADHD families.

Adolescent↗

PubMed2004

A novel polymorphism of the gene encoding furin, a TGF-beta1 activator, and the influence on cardiac allograft vasculopathy formation.

BACKGROUND: Coronary vasculopathy (CV) is an important determinant of survival following cardiac transplantation. We have previously shown that G915C polymorphism of the Transforming Growth Factor-beta1 (TGF-beta1) gene strongly influences CV development. Furin is a proprotein convertase enzyme important in TGF-beta1 activation. We investigated for polymorphism within the promoter region of the gene for furin (fur). Allelic variation of the fur gene, in conjunction with TGF-beta1 polymorphism, was subsequently related to the development of CV. METHODS AND RESULTS: The fur gene promoter region (position -1199 to +39) was analysed by SSCP and sequencing. A C/T single nucleotide substitution polymorphism at position -231* was identified. Using PCR the fur and TGFB1 genotypes were identified in 115 cardiac transplant recipients. CV was diagnosed at routine surveillance post-transplant coronary angiography. Fur polymorphism had no influence on vasculopathy development; median time to diagnosis, *C/C homozygotes, 2.27 years (2.10-4.32), *C/T heterozygotes 2.97 years (2.09-4.24), *T/T homozygotes 2.65 years (2.33-4.08), (P=0.95). Allelic variation did not influence Kaplan Meier actuarial analysis of disease onset (P=0.54). Ninety-three percent of recipients were high TGF-beta1 producers. We used fur polymorphism to substratify patients with the +915*G/G TGFB1 (high producing) allele. Fur polymorphism did not influence CV development within this TGF-beta1 high producer cohort, when analysed by time to first diagnosis and Kaplan Meier testing. CONCLUSIONS: We have described a novel polymorphism at position -231* in the gene encoding furin. The fur -231* single nucleotide polymorphism in isolation, or in conjunction with TGFB1 polymorphism, is not useful as a genetic risk marker for cardiac transplant associated coronary vasculopathy.

Adult↗

PubMed2001

[Renin-angiotensin system genetic polymorphisms and essential hypertension in the Spanish population].

BACKGROUND: The goal of this study was to analyse the association between essential hypertension and the main genetic polymorphisms at the renin-angiotensin system in the Spanish population. PATIENTS AND METHOD: Case-control study including 185 essential hypertensive subjects(age [SD] 39.6 [7.5] years, 52% women, systolic blood pressure 151.2 [17.4] mmHg, diastolic blood pressure 96.0 [9.4] mmHg) and 350 sex- and age-matched normotensive individuals selected from a sample of the general population of the Comunidad Valenciana, Spain (age 39.4 [8.0] years, 51.7% women, systolic blood pressure 116.0 [12.0] mmHg, diastolic blood pressure 69.6 [8.5] mmHg). A PCR was performed to determine I/D angiotensin converting enzyme (ACE) gene polymorphism, A-6G and M235T angiotensinogen gene polymorphism and A1166C polymorphism of the angiotensin II type 1 receptor. RESULTS: There were no differences between cases and controls with regard to genotypic and allelic distributions. In hypertensive patients,there were no differences in genotypic or allelic distributions after considering the presence or absence of a familial history of hypertension or comparing tertiles of systolic and diastolic blood pressure values. Only in women, the combination of a C allele of A1166C polymorphism with an A-6G angiotensinogen polymorphism A allele (p = 0.007), or an M235T angiotensinogen polymorphism T allele (p = 0.007), was associated with a higher risk of hypertension. CONCLUSIONS: We found no association between essential hypertension risk and I/D ACE gene, M235T and A-6G angiotensinogen gene, or A1166C angiotensin II type 1 receptor gene polymorphisms. An epistatic effect was observed in young women between angiotensin II type 1 receptor polymorphisms and angiotensinogen polymorphisms.

Adolescent↗

PubMed2003

In vitro characterization of a human calcitonin receptor gene polymorphism.

Calcitonin is a 32 amino acid peptide hormone that inhibits bone resorption by stimulating calcitonin receptors (CTR) located on the surfaces of osteoclasts. A polymorphism at nucleotide 1340 of the human calcitonin receptor gene (CALCR) lies within the coding region and has the potential to change the amino acid at codon 447 from leucine to proline. In the present study, we scanned the coding region, portions of the 5'-flanking and 3'-flanking sequences, and the intron-exon boundaries of the human CALCR gene for additional polymorphisms, and determined the frequency of the codon 447 polymorphism in several ethnic groups. Because a leucine to proline change has the potential for significant structural alteration, receptor genes encoding either leucine or proline at residue 447 were transiently expressed in COS-7 cells to determine the binding and functional consequences of this polymorphism. Our complete polymorphism scan of the CALCR gene identified 11 polymorphic sites in the gene and confirmed the presence of the previously identified nucleotide T1340C (codon 447) polymorphism. Ten of the 11 polymorphisms were single nucleotide polymorphisms (SNPs). For the codon 447 polymorphism, the prevalence of the TT genotype (leucine) was 59% in Caucasians, 27% in African-Americans, 0% in Asians, and 20% in Hispanics. The presence of this SNP appears to have no statistically significant difference with the receptor's ability to bind calcitonin or signal when activated with the hormone.

Analysis of Variance↗

PubMed2001

Polymorphisms within the interleukin-1 beta gene cluster and preeclampsia.

OBJECTIVE: To identify associations between polymorphisms within the interleukin-1 beta gene cluster, all of which increase protein expression, and preeclampsia. METHODS: We genotyped a Hispanic population (69 women with preeclampsia and 47 controls) for two polymorphisms of the interleukin-1 beta gene (promoter region and exon 5) and one polymorphism of the interleukin-1 receptor antagonist gene in intron 2. Clinical data were collected from medical records. Values are given as means or medians. Statistical power to identify a difference in occurrence of interleukin-1 beta promoter, interleukin-1 beta exon 5, and interleukin-1 receptor antagonist gene polymorphisms in women with preeclampsia compared with controls was 21%, 15.9%, and 30.9%, respectively. RESULTS: We found no association between any single polymorphism and occurrence of preeclampsia. Among women with preeclampsia, those with polymorphism of interleukin-1 receptor antagonist gene had higher mean systolic blood pressure (BP) at admission (178 +/- 33.4 versus 159 +/- 19.5 mmHg, P =.039). When all three polymorphisms combined were evaluated, women with preeclampsia and at least three mutant alleles (n = 8) had higher mean systolic BP at admission (182 +/- 30 versus 160 +/- 20.5 mmHg, P =.009) and increased alanine aminotransferase (67 [10--1024] versus 20 [3--407] IU/L, P =.04) and aspartate aminotransferase (119 [25--2239] versus 24 [4--489] IU/L, P =.002). At admission, BP in controls was independent of any polymorphism identified. CONCLUSION: Although the power of this study was limited, our data do not support a role for polymorphisms of the interleukin-1 beta and interleukin-1 receptor antagonist genes in the pathogenesis of preeclampsia among Hispanic women. Our findings do suggest that polymorphisms within the gene cluster might influence severity of preeclampsia.

Adult↗

PubMed2002

Serotonin transporter gene polymorphism influences age at onset in patients with bipolar affective disorder.

Serotonin transporter (SLC6A4) gene polymorphism is associated with several behavioral and psychiatric traits. In bipolar affective disorder, two polymorphisms of the SLC6A4 gene, a variable number of tandem repeats in the second intron and a 44 bp insertion/deletion in the serotonin transporter gene linked polymorphic region (5-HTTLPR), have been extensively studied. The findings are conflicting possibly because of the heterogeneity of bipolar disorder. Early-onset bipolar disorder appears to be clinically and genetically more homogeneous and was recently suggested to be associated with the 5-HTTLPR polymorphism. We tested the association between two polymorphisms of the SLC6A4 gene and age at onset (AAO) in a sample of bipolar patients. For both SLC6A4 gene polymorphisms, AAO of subjects with different genotypes were compared. SLC6A4 genotype distributions of different AAO groups were also compared. The variable number of tandem repeats (VNTR) polymorphism significantly influences the AAO but the serotonin transporter gene linked polymorphic region (5-HTTLPR) polymorphism did not. Patients carrying at least one VNTR STin2.12 allele began their illness later whereas patients carrying the 'ss' genotype tended to begin their illness earlier. Differential sampling procedures may influence the proportion of AAO subgroups in a given association study, and therefore these results may explain the conflicting results obtained in studies of the association between the SLC6A4 gene polymorphism and bipolar affective disorder (BPAD).

Adolescent↗

PubMed2001

Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension.

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.

Adult↗

PubMed2003

Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia.

BACKGROUND: Genetic polymorphisms of steroid 5alpha-reductase have been studied in androgenetic alopecia in Caucasians, but the genes encoding the two isoenzymes were not associated with male pattern baldness. Genetic polymorphisms and ethnic variations have not been studied for Asians, although it is suggested that racial difference could exist and influence clinical phenotypes. OBJECTIVE: The purpose of our study is to investigate the genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 (SRD5A1 and SRD5A2) genes in Korean population, and to study the association of these polymorphisms with the development, clinical types (female or male pattern) and therapeutic response of androgenetic alopecia. METHODS: Sixty-six patients with androgenetic alopecia and controls consisted of 92 healthy men were included. Twenty-four patients were treated with finasteride for at least 6 months, and clinical responses were assessed by a simple classification. For type 1 isoenzyme, HinfI and NspI restriction fragment length polymorphisms (RFLPs) were detected using polymerase chain reaction method. For type 2 isoenzyme, RsaI RFLPs detected valine/leucine polymorphisms at codon 89, and MowI RFLPs detected alanine/threonine polymorphisms at codon 49. RESULTS: We could not find any significant associations of the genetic polymorphisms of these two isoenzyme genes with androgenetic alopecia in Koreans (P>0.05). These polymorphisms were not associated with the clinical types of baldness or the response to finasteride (P>0.05). CONCLUSION: These results suggest that polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2001

Association of polymorphism of methylene-tetrahydro-folate-reductase with urinary albumin excretion rate in type 1 diabetes mellitus but not with preeclampsia, retinopathy, and preterm delivery.

AIM: The genetic setting is a potential risk factor for dysfunction of vascular endothelial cells. The prevalence of polymorphism in the methylene-tetrahydro-folate-reductase (MTHFR) gene (677C-->T) was evaluated in diabetic pregnancy complicated by preeclampsia, nephropathy, retinopathy, and preterm delivery. The role of hyperhomocysteinemia in microangiopathy in diabetes mellitus has been debated and is mainly seen with reduced activity of the MTHFR gene. A polymorphism in the gene for MTHFR is identified causing this phenomenon. DESIGN: Two hundred and sixty-eight pregnant women with type 1 diabetes mellitus were recruited. Two hundred and thirty-three women were successfully analyzed for MTHFR gene polymorphism 677C-->T and compared to the incidence of the polymorphism in the background population (n=1084). The pregnancy data charts were reviewed retrospectively. RESULTS: The frequency of the MTHFR polymorphism in the background population was 29% and the heterozygozity 42%. The women with type 1 diabetes mellitus had a higher frequency of the MTHFR polymorphism with 52% heterozygotes and 9% homozygotes than had the background population (heterozygotes, background vs. type 1 diabetes mellitus: chi(2)=14, df=1, p<0.0002). The odds ratio for heterozygozity of the MTHFR polymorphism was 1.8 (95% Cl: 1.3-2.4) in women with type 1 diabetes mellitus. Women with either micro- or macroalbuminuria had a higher frequency of MTHFR polymorphism with 61% heterozygotes and 3% homozygotes than had the background population (heterozygotes: chi(2)=8.9, df=1, p<0.01). The odds ratio for heterozygozity of the MTHFR polymorphism was 2.3 (95% CI: 1.4-4) in women with type 1 diabetes mellitus. CONCLUSION: An association was demonstrated between the MTHFR polymorphism and type 1 diabetes mellitus as well as increasing albumin excretion rate in pregnant women.

Albuminuria↗

PubMed1999

The number of platelet glycoprotein Ia molecules is associated with the genetically linked 807 C/T and HPA-5 polymorphisms.

BACKGROUND: The neutral 807 C/T (Phe224) polymorphism (807 C/T polymorphism) of the glycoprotein (GP)Ia gene has been recently associated with the number of GPIa molecules on the platelet surface. The association of the number of GPIa molecules with other GPIa polymorphisms, such as HPA-5 (Glu/Lys505) (HPA-5 polymorphism), involved in alloimmune thrombocytopenias is unknown. STUDY DESIGN AND METHODS: The association of the HPA-5 polymorphism with the number of GPIa molecules on the platelet surface in 159 white blood donors was investigated. The genetic linkage between the HPA-5 and the 807 C/T polymorphisms in 316 individuals was also determined. RESULTS: Both the 807 C/T and HPA-5 polymorphisms correlate with the number of GPIa molecules on the platelet surface. The 807 T and HPA-5b alleles are associated with increased numbers of GPIa molecules on the platelet surface. Moreover, the HPA-5b allele is genetically linked to 15.8 percent of the 807 C alleles. Therefore, the number of GPIa molecules on the platelet surface is dependent on both GPIa polymorphisms as follows: 807 T/T, HPA-5 a/a > 807 C/T, HPA-5 a/b > 807 C/T, HPA-5 a/a > 807 C/C, HPA-5 a/b > 807 C/C, HPA-5 a/a. CONCLUSION: Two GPIa polymorphisms (807 C/T and HPA-5) responsible for the variability in the numbers of GPIa/IIa molecules on the platelet surface in whites have been identified. Despite the genetic linkage between the two polymorphisms, their influence on the number of GPIa molecules on the platelet surface may occur through different mechanisms.

Adult↗

PubMed2001

The association of microsomal epoxide hydrolase polymorphisms and lung cancer risk in African-Americans and Mexican-Americans.

This study evaluated the influence of genetic polymorphisms in the microsomal epoxide hydrolase (mEPHX) gene on lung cancer risk in a case-control study of two different ethnic groups, Mexican-Americans and African-Americans. There were 138 lung cancer cases (60 Mexican-American and 78 African-American) and 148 controls (76 Mexican-American and 72 African-American). There was a significant difference in the distribution of the mEPHX exon 4 polymorphism between the two ethnic groups with African-Americans more likely to be heterozygous and Mexican-Americans to be wild-type. There was no significant difference between the ethnic groups for the allelic distribution of the mEPHX exon 3 polymorphism. When the exon 4 and exon 3 polymorphism distributions in cases and controls were examined by ethnicity, only the Mexican-American cases showed a substantial proportion with the exon 4 polymorphism. The exon 4 polymorphism was associated with a significantly increased risk of lung cancer only among the Mexican-American cases (adjusted OR 3.6, 95% CI 1.26, 10.42). Younger Mexican-Americans with the exon 4 polymorphism had a greater risk of lung cancer than older members of their groups (adjusted OR 7.4, 95% CI 1.36, 40.23; 1.6, 95% CI 0.33, 7.80, respectively). The exon 3 polymorphism did not appear to significantly increase the risk of lung cancer in all but one study group examined. Mexican-Americans younger than 65 years did demonstrate an elevated risk of lung cancer (adjusted OR 4.6, 95% CI 1.19, 17.56). However, no statistically significant risk was observed in the African-American study groups for both exon 3 and exon 4 polymorphisms. These findings suggest that the presence of the exon 4 and exon 3 polymorphisms of mEPHX may be associated with an increased risk of lung cancer particularly among younger Mexican-Americans in this study.

Aged↗