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Results for “polymorphisms”

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PubMed2003

Vascular endothelial growth factor gene polymorphisms in Japanese patients with sarcoidosis.

OBJECTIVES: Vascular endothelial growth factor (VEGF) promotes angiogenesis, mediates vascular permeability, and activates and recruits monocytes. VEGF is produced in activated alveolar macrophages, in epithelioid cells, and in multinuclear giant cells of pulmonary sarcoid granulomas. Recent reports have shown that a polymorphism at - 627 of the VEGF gene is related to VEGF protein production, and a polymorphism at + 813 is associated with VEGF plasma levels. We investigated the roles of such polymorphisms in the development and extent of sarcoidosis. METHODS: We examined polymorphisms of the VEGF gene in 103 Japanese patients with sarcoidosis and 146 healthy Japanese control subjects. The position - 627 polymorphism was determined using the TaqMan (TaqMan Laboratory, University of Pittsburgh Cancer Institute; Pittsburgh, PA) polymerase chain reaction (PCR) method. For genotyping of the position + 813 polymorphism, the PCR restriction fragment length polymorphism method was performed. RESULTS: As for + 813 genotypes, the less-common genotypes CT and TT were found more often in control subjects than in patients (odds ratio, 0.490; 95% confidence interval, 0.276 to 0.868). A significant increase in the frequency of the T allele (p = 0.005, Pc = 0.020 after Bonferroni correction) was observed in control subjects. As for - 627 genotypes, the mean value of the FEV(1)/FVC percentage in GG type was lower than that in CC or CG type, however, the other clinical findings did not suggest airway diseases in the GG type. CONCLUSIONS: We suggest that in VEGF gene polymorphisms the T allele at + 813 may decrease susceptibility to sarcoidosis.

Adult↗

PubMed2006

Interleukin-12B gene polymorphism does not confer susceptibility to Graves' ophthalmopathy in Japanese population.

Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction--restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

Adolescent↗

PubMed2000

Association of the apolipoprotein B gene polymorphisms with cholesterol levels and response to fluvastatin in Brazilian individuals with high risk for coronary heart disease.

The influence of genetic polymorphism of the apolipoprotein B on lipid metabolism and coronary heart disease (CHD) risk has been demonstrated in different populations, but few studies have shown the contribution of this risk factor in individuals from Brazil. The Ins/del, Xbal and EcoRI polymorphisms of apo B were evaluated in 93 controls and in 104 Caucasian individuals presenting with a high risk lipid profile (HR1) for CHD; 54 of these subjects (HR2) were treated with fluvastatin during 16 weeks. DNA polymorphisms of the apo B gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The X(-)X(-) genotype for Xbal polymorphism was associated with higher serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (p<0.01) in women of the HR1 group. The Ins/del and EcoRI polymorphisms were not associated with variation of lipid profile. After treatment with fluvastatin, TC and LDL-C levels of HR2 individuals were reduced by 23% and 30%, respectively. Individuals with II genotype had significantly greater reduction (34%) of LDL-C than those with ID/DD genotypes (27%). These results indicate that the Xbal polymorphism is associated with variation of serum TC and LDL-C levels in Brazilian women with lipid profile of risk for CHD and the Ins/del polymorphism is associated with the therapeutic response to fluvastatin.

Adult↗

PubMed2006

Frequency of a single nucleotide (A2317G) and 56-bp variable number of tandem repeat polymorphisms within the deoxyribonuclease I gene in five ethnic populations.

BACKGROUND: The single nucleotide polymorphism (SNP) at deoxyribonuclease I (DNase I), designated as DNASE1 (NCBI SNP number; 1053874), in exon 8 (A2317G) is considered to be one of the susceptibility genes for gastric and colorectal carcinoma and myocardial infarction. Recently, the presence of a variable number of tandem repeat (VNTR) polymorphisms, designated as HumDN1, in intron 4 was found. METHODS: Simultaneous genotyping of the DNASE1 and HumDN1 polymorphisms within the DNase I gene was performed in Ovambo, Turkish, Mongolian, Korean, and Japanese populations. RESULTS: The allele frequencies of the DNASE1 and HumDN1 loci differed among five populations. There was general uniformity for the two polymorphisms in the three Asian populations, but significant differences in genotype distribution between the Ovambo and Turkish populations. The DNASE1 *1 and HumDN1 *3 alleles were found to be the most predominant among the Ovambos. Turks had the highest allele frequency for DNASE1 *2, HumDN1 *4, and HumDN1 *5. A linkage disequilibrium between the single-nucleotide (A2317G) and 56-bp VNTR polymorphisms was revealed in all populations except the Ovambos. CONCLUSIONS: This study is the first to demonstrate the simultaneous genotyping of DNASE1 and HumDN1 polymorphisms and reveal the existence of a certain genetic heterogeneity in the worldwide distribution of these two polymorphisms. The combination of the two polymorphisms within a DNase I gene may be potentially useful for clinical purposes and in population genetic studies.

Asian People↗

PubMed2006

Association between an IGF-I gene polymorphism and body fatness: differences between generations.

OBJECTIVE: A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, body height and birth weight. In this study, we investigated whether this polymorphism is associated with body composition in young healthy subjects in two cohorts of different generations. DESIGN: Observational study with repeated measurements. METHODS: The study group consisted of two comparable young Dutch cohorts with a generational difference of around 20 years. The older cohort consisted of 359 subjects born between 1961 and 1965. Measurements were performed from 13 until 36 years of age. The younger cohort consisted of 258 subjects born between 1981 and 1989. Measurements were performed from 8 until 14 years of age. Height, body mass index (BMI), fat mass, fat-free mass, waist and hip circumference were compared between wild-type carriers and variant type carriers of the IGF-I polymorphism. RESULTS: In the younger cohort, body weight, BMI, fat mass and waist circumference were significantly higher in female variant carriers of the IGF-I polymorphism. A similar trend was observed in male variant carriers. In contrast, these differences were not observed in the older cohort. Irrespective of genotype, the younger cohort showed a significantly higher total fat mass, body weight and BMI compared with the older cohort. CONCLUSIONS: Because the differences between both genotypes were small, it seems likely that the genetic variability due to this IGF-I polymorphism impacts only slightly on body composition. Importantly, our study suggested that associations between this IGF-I promoter polymorphism and body composition possibly reflect a gene-environmental interaction of this polymorphism and that an environment that promotes obesity leads to a slightly more pronounced fat accumulation in variant carriers of this IGF-I polymorphism.

Adolescent↗

PubMed2006

Evaluation of clinical parameters and estrogen receptor alpha gene polymorphisms for patients with endometriosis.

Endometriosis is a chronic inflammatory disease, which is especially found in women with subfertility problems with an incidence of up to 30%. The disease is considered an estrogen-dependent disorder, where DNA polymorphisms of the estrogen receptor alpha (ERalpha) in connection with endometriosis are controversially discussed. From a German population of women, clinical data associated with the disease, including the American Fertility Society (AFS) I-IV classification, and non-clinical parameters were evaluated statistically in endometriosis patients (n = 98) and in control women (n = 98) without endometriosis. Using a multivariate statistical analysis, significant associations of endometriosis with dysmenorrhea (P < 0.001) and allergies against medicaments (P = 0.042) were found. A positive trend between first grade family history of endometriosis and allergies against medicaments was also observed, suggesting a genetic relationship. From both collectives, DNA from peripheral blood was analyzed for the frequency of the ERalpha DNA polymorphisms Xba1 (A/G) and PvuII (T/C) in intron 1 and the ERalpha exonic DNA polymorphism (G229A) with an amino acid exchange (Gly77Ser) in the transactivation domain. DNA samples from endometriosis lesions and control tissues from the same collectives were also analyzed for the exonic G229A polymorphism. Only homozygote wild-type alleles for the polymorphism G229A were found, making it a rare polymorphism in mid-European individuals. Allele types for the PvuII and Xba1 polymorphisms were analyzed with the observed statistically significant clinical parameters and showed no significant association with endometriosis; however a trend with AFS IV was noted, which could contribute to lesion severity. In conclusion, the analyzed polymorphisms in the ERalpha do not have a functional role concerning specific clinical parameters associated with endometriosis.

Adolescent↗

PubMed1998

Characterization of two polymorphic sites in the human kinin B1 receptor gene: altered frequency of an allele in patients with a history of end-stage renal failure.

On the basis of the genomic structure of the human B1 receptor (B1R) for kinins, the presence of possible allelic polymorphisms of this gene was investigated using restriction fragment-length polymorphism and single-strand conformation polymorphism. The frequencies of the found alleles were determined in healthy volunteers and in patients with a history of end-stage renal failure, because there is evidence for a nephroprotective action of the kallikrein-kinin system. An A1098-->G polymorphism has been identified in exon 3 in a minority of volunteer blood donors, and is located 35 nucleotides downstream from the stop codon and 14 nucleotides upstream from the polyadenylation signal. The frequency of the G allele is 4.4% in the control sample and not significantly altered in patients with a history of end-stage renal failure. A second and more frequent polymorphism (18.1% of the alleles in the control group, prevalence of 33.3%) consists of a single base substitution (G-699-->C) in the putative promoter region. This polymorphism is significantly less frequent in the population of renal failure patients (prevalence of 20.6%) and determines an increased activity of the promoter function in constructions involving a reporter gene. The altered prevalence of this allele was also found in some etiologic subgroups of uremic patients. This study confirms the mapping of the B1R gene to 14q32. Other investigators have mapped the bradykinin B2 receptor (B2R) gene to a close site on human chromosome 14. A previously described B2R polymorphism (exon 2, C181-->T) had an allele frequency of 9.7% in the control sample and appears to be clinically neutral. The polymorphism of the B1R promoter may be a marker of prognostic significance for the preservation of renal function in diseased individuals.

Adult↗

PubMed2006

Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study.

OBJECTIVES: To assess the influence of the serotonin transporter variable number of tandem repeat (HTT-VNTR) polymorphism and the serotonin transporter-gene-linked polymorphic region (HTTLPR) polymorphism on development of side effects under antidepressant therapy. METHODS: A total of 109 depressive in-patients treated with various antidepressants according to local clinical practice were included in the investigation. Four weeks after admission to hospital, side effects were assessed by using a modified version of the dosage record and treatment emergent symptoms scale (DOTES). Differences in side effects between the genotype groups of both polymorphisms were analyzed using the Fisher's exact test. RESULTS: A total of 65 patients received mirtazapine (25 of them in combination with other antidepressants), and 44 patients were predominantly treated with antidepressants acting via HTT, such as selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). When patients were treated with HTT-blocking antidepressants, a significantly higher occurrence of side effects in patients with the HTTVNTR 2.10/2.10 genotype (52.6%) than in patients with the 2.10/2.12 (12.5%) and 2.12/2.12 (0%) genotypes (p = 0.004) was found. With regard to the HTTLPR polymorphism, patients predominantly on HTT-blocking antidepressants with the s/s genotype suffered more frequently from side effects (50.0%) than heterozygotes (40.0%) and homozygotes for the l-allele (0%) (p = 0.002). In contrast, no association of the HTTVNTR polymorphism was found in patients treated with mirtazapine. The risk groups defined by a combined genotype from both polymorphisms demonstrated a major effect on the incidence of adverse drug events in patients treated with predominantly HTT-blocking antidepressants (p = 0.00018; low risk: 0%, 0/13, medium risk: 13.3%, 2/15, high risk: 62.5%, 10/16). CONCLUSION: These results support the hypothesis that both polymorphisms influence tolerability to drugs primarily acting via HTT inhibition, such as SSRIs, TCAs and venlafaxine. Tolerability to mirtazapine was not influenced, probably owing to a different mode of action. As there are limitations due to the heterogeneity of treatment and concomitant therapy, further studies are required to confirm the obtained results.

Adolescent↗

PubMed1985

New polymorphisms at the insulin locus increase its usefulness as a genetic marker.

Polymorphic sites adjacent to known genes can be used to examine the segregation of a disease relative to that gene in families, or to map the gene of interest relative to other loci. The polymorphic region 5' to the human insulin gene (5' FP) permits such analysis, but the three size classes previously identified are insufficient for many studies. More alleles are identified with restriction enzymes that generate small fragments (Pvu II). Nonetheless, sufficient polymorphism for informative family analyses is often not present. To facilitate such analyses, we searched for other polymorphisms in over 20 KB of DNA at the insulin locus in Pima Indians, American Blacks, and Caucasians. The previously described allelic variant at a Pst I site in the 3'-untranslated portion of the gene was not polymorphic in any race. An upstream Hinc II site (-62 BP) was present in only 48% of Black alleles, but was not polymorphic in Pima Indians or Caucasians. New polymorphisms were found at a Taq I site (-11,000 BP) and a Rsa I site (-13,000 BP). The Taq I site was present in 89% of Black alleles, 87% of Pima Indian alleles, and 84% of Caucasian alleles. In contrast, the Rsa I site was present in 60% of Black and Caucasian alleles, but in only 47% of Pima Indian alleles. The Hinc II, Rsa I, and Taq I sites show no obvious linkage with each other or the 5' FP. A fourth polymorphism, previously identified with Sac I, was found to be the creation of a new Sac I site at +2500 BP in 10% of Black alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed2000

Polymorphism of drug-metabolizing enzymes in relation to individual susceptibility to industrial chemicals.

Polymorphism and the induction/inhibition of drug-metabolizing enzymes, such as cytochrome P450, aldehyde dehydrogenase (ALDH), glutathione S-transferase (GST), N-acetyltransferase (NAT), and NAD(P)H-quinone oxidoreductase (NQO1), were reviewed in relation to susceptibility to disease and to inter-individual difference in biological monitorings. A number of genetic and acquired factors can influence the susceptibility of an individual to chemicals, creating a so-called predisposition. Most cases in which genetic factors were present resulted from polymorphism of drug-metabolizing enzymes. However, conflicting reports have appeared on the relationship between polymorphism and risk of disease; in some cases, biologically plausible mechanisms linking genotypes and disease are not yet in evidence. Current findings based on biological monitoring of chemicals are insufficient to evaluate the relationship between genetic polymorphism and acquired risk when exposure has occurred in an occupational area. Investigation of such situations has generated data implicating GSTT1, GSTM1, NAT2, and NQO1 polymorphisms in biological monitoring of some chemicals; the ALDH2 polymorphism is the likely link between the genotype and the metabolism of low molecular aliphatic aldehydes. Although this polymorphism is limited in the case of Japanese as well as other Asian subjects, the inhibitors of ALDH2 activity such as trichloroethylene may produce a false polymorphism of this gene. As to the effect of factors influencing acquired predisposition, such as ethanol intake, intake of low carbohydrate diet or diabetes, corroborative epidemiological studies may be further required.

Aldehyde Dehydrogenase↗

PubMed2004

Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.

The Pit-1 gene was studied as a candidate for genetic markers of growth and carcass traits. Angus beef cattle that were divergently selected for high- or low-blood serum IGF-I concentration were used in this study. The single-strand conformation polymorphism method was used to identify polymorphism in the Pit-1 gene including regions from intron 2 to exon 6. Two polymorphisms, Pit1I3H (HinfI) and Pit1I3NL (NlaIII), were detected in intron 3 of the Pit-1 gene. One polymorphism, Pit1I4N (BstNI), was found in intron 4, and a single nucleotide polymorphism, Pit1I5, was found in intron 5. The previously reported polymorphism in exon 6, Pit1E6H (HinfI), was also studied in 416 Angus beef cattle. Associations of the polymorphisms with growth traits, carcass traits, and IGF-I concentration were analyzed using a general linear model procedure. No significant associations were observed between these polymorphisms and growth and carcass traits.

Animals↗

PubMed2006

Gly395Arg polymorphism of PPARalpha gene was not detected in Japanese population of 729 individuals.

Peroxisome proliferator-activated receptor a (PPARalpha) is a member of the nuclear receptor superfamily and participates in the regulation of key proteins involved in lipid metabolism, fatty acid oxidation, homeostasis, and inflammation. Several polymorphisms of the human PPARalpha gene, such as Leu162Val polymorphism and Val227Ala polymorphism, have been described in different races. Recently, another PPARalpha polymorphism Gly395Arg polymorphism has been reported in Caucasian and African subjects. Using the Invader assay, we searched for this polymorphism in 729 Japanese adults randomly selected in a rural population. Although the synthesized oligonucleotides of each polymorphism could be distinguished clearly, all 729 individuals had the Gly (G) allele and none had the Arg (C) allele. These data suggest that there is racial variability in the frequencies of PPARalpha gene polymorphisms.

Adult↗

PubMed2004

Expression of p21(WAF1) and p53 and polymorphism of p21(WAF1) gene in gastric carcinoma.

AIM: To investigate the relationship between expression of p21(WAF1) and p53 gene, and to evaluate the deletion and polymorphism of p21(WAF1) gene in gastric carcinoma (GC). METHODS: Expression of p21 and p53 proteins, and deletion and polymorphism of p21 gene in GC were examined by streptavidin-peroxidase conjugated method (SP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS: The expression of p21 and p53 was found in 100% (20/20) and 0% (0/20) of normal gastric mucosae(NGM), 92.5% (37/40) and 15.0% (6/40) of dysplasia (DP) and 39.8% (43/108) and 56.5% (61/108) of GC, respectively. The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05), while the positive rate of p53 in GC was higher than that in NGM and DP (P<0.05). p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30), 35.0% (14/40) and 77.5% (31/40), 26.7% (4/15) and 80.0% (12/15), 30.8% (4/13) and 30.8% (4/13), and 20.0% (2/10) and 30.0% (3/10) of well-differentiated, poorly-differentiated, undifferentiated carcinomas, mucoid carcinomas and signet ring cell carcinomas. The expression of p21 in well-differentiated carcinomas was significantly higher than that in poorly-differentiated, un-differentiated, mucoid carcinomas and signet ring cell carcinomas (P<0.05). Contrarily, The expression of p53 was increased from well-differentiated to poorly-differentiated and un-differentiated carcinomas (P<0.05). The expression of p21 and p53 in paired primary and metastatic GC (35.3% and 70.6%) was different from non-metastatic GC (62.5% and 42.5%) markedly (P<0.05). The expression of p21 in invasive superficial muscle (60.0%) was higher than that in invasive deep muscle or total layer (35.2%) (P<0.05) and was higher in TNM stages I (60.0%) and II (56.2%) than in stages III (27.9%) and IV (22.2%) (P<0.05), whereas the expression of p53 did not correlate to invasion depth or TNM staging (P>0.05). The exoression patterns of p53+/p21-, and of p53-/p21+ were found in 5.0% and 82.5% of DP. There was a significant correlation between expression of p21 and p53 (P<0.05). But there was no significant correlation between expression of both in GC (P>0.05). There was no deletion in exon 2 of p21 gene in 30 cases of GC and 45 cases of non-GC, but polymorphism of p21 gene at exon 2 was found in 26.7% (8/30) of GC and 8.9% (4/45) of non-GC, a significant difference was found between GC and non-GC (P<0.05). There was no significant relation between p21 expression of polymorphism (37.5%, 3/8) and non-polymorphism (45.5%, 10/22) in GC (P>0.05). CONCLUSION: The loss of p21 protein and abnormal expression of p53 are related to carcinogenesis, differentiation and metastasis of GC. The expression of p21 is related to invasion and clinical staging in GC intimately. The expression of p21 protein depends on p53 protein largely in NGM and DP, but not in GC. No deletion of p21 gene in exon 2 can be found in GC. The polymorphism of p21 gene might be involved in gastric carcinogenesis.There is no significant association between polymorphism of p21 gene and expression of p21 protein.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed2006

Relationship between IFN-gamma gene polymorphism and susceptibility to intrauterine HBV infection.

AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-gamma gene polymorphism, including IFN-gamma+874A/T single nucleotide polymorphism (SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-gamma+874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group (group I) and the normal immune children group (group II). Capillary electrophoresis was performed in the above two groups to assay the IFN-gamma CA repeat microsatellite polymorphism. RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-gamma+874 genotype between the two groups (chi2 = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-gamma+874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-gamma+874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.238, P = 0.02389, OR = 2.228, 95% CI = 1.244-3.992). (CA12)+/(CA12)+ of IFN-gamma CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups (chi2 = 5.64, P = 0.0176). Frequency of IFN-gamma CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-gamma CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.548, P = 0.0060). CONCLUSION: There is a relationship between IFN-gamma+874A/T SNP and intrauterine HBV infection as well as between IFN-gamma CA microsatellite polymorphism and intrauterine HBV infection. IFN-gamma gene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection.

Alleles↗

PubMed2005

Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000.

We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G --> A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (-514 --> CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.

Apolipoprotein C-III↗

PubMed1999

DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit--is there a relation with the low risk of cardiovascular disease in the Inuit?

Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared with Caucasian populations. We have extended this study and evaluated whether or not this was also true for the genetic polymorphisms of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin-converting enzyme (ACE) and angiotensinogen in a group of 133 Greenland Inuit, aged 30-34 gamma. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians. In the Inuit, the f(insertion allele) of the t-PA intron8ins311 polymorphism was 0.37 (CI 0.32-0.43), the f(4G allele) of the PAI-1 promoter polymorphism was 0.88 (CI 0.83-0.91), the f(deletion allele) of the ACE intron16ins287 polymorphism was 0.40 (CI 0.33-0.47) and the f(M-allele) of the angiotensinogen M/T353 polymorphism was 0.30(CI 0.25-0.38). As for fibrinogen and FVII polymorphisms, these frequencies are all significantly different from what is reported for Caucasian populations. In the Inuit, plasma levels of fibrinogen and D-Dimer were higher than in the Danes, the PAI-1 levels were lower and FVII, t-PA and CRP levels were comparable. The observed allele frequencies of the polymorphisms of t-PA, fibrinogen, FVII, ACE, angiotensinogen and the plasma levels of PAI-1 and D-Dimer were in accordance with the low CVD risk in the Inuit, considering the observed associations between these measures and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA). In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared with Caucasian populations, and these differences were sometimes, but not always, in accordance with the observed low cardiovascular disease risk of the Inuit population.

Adult↗

PubMed2000

Characteristics of myotonic dystrophy in Istria: molecular genetic approach. Part II: Analysis of genetic polymorphisms.

One of the world highest prevalence estimates of myotonic dystrophy (DM) has been reported in the Croatian region Istria. To analyse the population genetic characteristics of DM locus in Istria, two intragenic and three extragenic polymorphic markers were tested. The Southern blot technique was used for D19S63 locus analysis, whereas PCR analysis was performed for CKMM, Alu polymorphism, DMPK (G/T) intron 9/HinfI polymorphism, and D19S207 genetic markers. The compound haplotypes segregating with DM were established. A complete association between the DM mutation and D19S63, D19S207, intron 9/HinfI polymorphism and Alu polymorphism markers were found. In all DM chromosomes: D19S63 and Alu markers had the allele 1 in common; D19S207 had the allele 3 in common, DMPK (G/T) intron 9/HinfI marker had the allele 2 in common. The analysis of CKMM polymorphism revealed genotype heterogeneity; in DM chromosomes either allele 2 or allele 4 were found. The haplotype analysis in the population of Croatian Istria supports the linkage disequilibrium between the DM mutation and Alu polymorphism, intron 9/HinfI polymorphism, D19S63 and D19S207 markers as reported worldwide. The results of the haplotype analysis suggest a common origin of the mutation in Istrian population.

Adult↗

PubMed2001

Etiology of differences in hematocrit between males and females: sequence-based polymorphisms in erythropoietin and its receptor.

INTRODUCTION: Males have a higher hematocrit (Hct) than females. The cause of this gender-based difference is unclear. We sought to determine whether polymorphisms of the erythropoietin (EPO) gene or of its receptor (EPOR) explain this situation. METHODS: We designed primers for the EPO and EPOR genes. Previously undescribed polymorphisms were found based on band migration on polyacrylamide gel, and when then sequenced. The distribution of these polymorphisms was studied in a population of 819 non-iron-deficient, healthy blood donors. To test the gender differences, analysis was done based on groups defined by Hct levels. The chi-square statistic was used to compare the frequency differences between groups, with P < .05 considered statistically significant. RESULTS: We found previously reported polymorphisms in both the EPO and EPOR genes. Sequence analysis showed that the EPO polymorphism was due to a difference in the repeat copy number of the tetranucleotide cytosine adenine cytosine thymine (CACT) at position 2153. A previously undescribed 12th allele was found for the EPOR polymorphic site. Statistical analysis showed that the EPOR alleles, EPORA1 and EPORA10, were present at a significantly higher frequency in females than in males (P = .027 and P = .041, respectively), and EPOR5 was found less frequently in females than in males (P = .048). The allelic frequency of the EPO polymorphism was not significantly different by gender or Hct groups. DISCUSSION: These results suggest that the variation of Hct level by gender may have a genetic basis. The sequence-based polymorphism for EPOR may be partly responsible for this gender-based variation in Hct level. These findings offer new clues to understanding Hct variation in the general population and to elucidating mechanisms of controlling Hct levels.

Adult↗