PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “intronic polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2004

'Interleukin-4 gene polymorphism and its relation to periodontal disease in a Brazilian population of African heritage'.

OBJECTIVES: Host modifying factors, such as genetic predisposition, may increase severity of periodontitis. Genetic polymorphisms in interleukin-4 (IL-4) genes seem to influence host response to microbial challenge. Two IL-4 polymorphisms were found in association with asthma and atopy, and later with aggressive periodontitis in Caucasians. There seems to be a trend for racial differences regarding polymorphisms. Therefore, this study aimed to evaluate if these IL-4 polymorphisms were associated with periodontal disease in a Brazilian population of African heritage. METHODS: Sixty patients were divided into two groups: periodontitis group (n = 30) and control group (n = 30) Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 bp repeat polymorphism in intron 2 and in the -590 position of the promoter region was performed through PCR-RFLP and electrophoresis in agarose gel. RESULTS: No significant differences were found in the genotype frequency of the polymorphisms between control and periodontitis group. Chi square test and Mann-Whitney test were used for statistical analysis. CONCLUSIONS: We concluded that the studied IL-4 polymorphisms were not related to periodontal disease susceptibility in this African-American Brazilian population.

Adolescent↗
PubMed2006

Association of interleukin-1Ra gene polymorphism in patients with bladder cancer: case control study from North India.

OBJECTIVES: To evaluate whether polymorphism of interleukin (IL)-1beta gene (exon 5 and promoter region) and IL-1 receptor antagonist (Ra), 86-bp variable number tandem repeat, are associated with transitional cell carcinoma of the urinary bladder, because cytokines have been hypothesized to be important in cancer development. METHODS: The study included 120 patients with bladder cancer (age range 32 to 69 years) and 150 age-matched controls (age range 25 to 62 years). The polymorphisms were identified by polymerase chain reaction/restriction fragment length polymorphism method and IL-1Ra polymorphism by variable number of identical tandem repeat analysis. Genotype distribution and allelic frequencies between patients and controls were compared. RESULTS: A significant difference was found in the frequency distribution of the IL-1Ra gene polymorphism in patients with bladder cancer compared with the normal control group (P < 0.001), but no difference was found in the frequencies of the IL-1beta promoter region and exon 5 genotypes between patients with bladder cancer and controls (P = 0.112 and P = 0.953, respectively). CONCLUSIONS: This is perhaps the first report on polymorphic changes in gene encoding IL-1Ra in patients with bladder cancer from India. Our data suggest that IL-1Ra intron 2 polymorphism seems to play a prominent role among the IL-1 gene cluster with respect to bladder cancer, and the association studies appear to be plausible in determining the cancer susceptibility and risk.

Adult↗
PubMed2002

Influence of the endothelial nitric oxide synthase polymorphism on the progression of autosomal dominant polycystic kidney disease and IgA nephropathy.

BACKGROUND: The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies--autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy. METHODS: We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group, we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 +/- 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele. RESULTS: The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN, the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9% (9/43) and 79.1% (38/43) in IgA with ESRF. CONCLUSION: Both in ADPKD and IGAN groups, there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOSa allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p < 0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.

Adult↗
PubMed1998

Re-examination of factors associated with expansion of CGG repeats using a single nucleotide polymorphism in FMR1.

In at least 98% of fragile X syndrome cases, the disease results from expansion of the CGG repeat in the 5' end of FMR1. The use of microsatellite markers in the FMR1 region has revealed a disparity of risk between haplotypes for CGG repeat expansion. Although instability appears to depend on both the haplotype and the AGG interspersion pattern of the repeat, these factors alone do not completely describe the molecular basis for the linkage disequilibrium between normal and fragile X chromosomes, in part due to instability of the marker loci themselves. In an effort to better understand the mechanism of dynamic mutagenesis, we have searched for and discovered a single nucleotide polymorphism in intron 1 of FMR1 and characterized this marker, called ATL1, in 564 normal and 152 fragile X chromosomes. The G allele of this marker is found in 40% of normal chromosomes, in contrast to 83% of fragile X chromosomes. Not only is the G allele exclusively linked to haplotypes over-represented in fragile X syndrome, but G allele chromosomes also appear to transition to instability at a higher rate on haplotypes negatively associated with risk of expansion. The two alleles of ATL1 also reveal a highly significant linkage disequilibrium between unstable chromosomes and the 5' end of the CGG repeat itself, specifically the position of the first AGG interruption. The data expand the number of haplotypes associated with FMR1 and specifically allow discrimination, by ATL1 alleles, of single haplotypes with differing predispositions to expansion. Such haplotypes should prove useful in further defining the mechanism of dynamic mutagenesis.

Adenine Nucleotides↗
PubMedDate not supplied

Carotid intima-media thickness and ACE-gene polymorphism in hemodialysis patients.

BACKGROUND: Carotid artery intima-media thickness (CIMT) has been used as a marker of atherosclerosis. An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with various cardiovascular diseases. This study is aimed at evaluating early atherosclerotic involvement of carotid vessels and the relation to known risk factors and ACE gene I/D in hemodialysis (HD) patients. METHODS: We measured CIMT using high-resolution B-mode ultrasonography in 51 non-diabetic HD patients and in 70 age- and sex-matched healthy controls, and evaluated the factors influencing CIMT. An I/D polymorphism in intron 16 of the gene coding for ACE was analysed by polymerase chain reaction. RESULTS: The mean CIMT was significantly higher in HD patients than in healthy subjects (p<0.0001). In multiple regression analysis, independent risk factors for increased CIMT in HD patients were predialysis systolic blood pressure (p<0.001) and ACE D allele (p<0.01). CONCLUSIONS: The present data suggest that CIMT is enlarged in HD patients. The ACE gene seems to be a candidate for influencing the CIMT and might therefore be involved in an HD patient's predisposition to the development of atherosclerosis.

Adolescent↗
PubMed2004

Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects.

BACKGROUND: Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic heart disease (IHD), but data from published studies with individually low statistical power are conflicting. To evaluate the role of polymorphisms in the eNOS gene in IHD, we considered all available studies in a meta-analysis. METHODS AND RESULTS: Case-control studies evaluating the association between the Glu298Asp, -786T>C, and intron-4 polymorphisms and IHD were searched in MEDLINE and EMBASE up to January 2003. The principal prior hypothesis was that homozygosity for eNOS Asp298, the -786C allele in the promoter, or the intron-4 (a allele) would be associated with an increased risk of IHD. Data were available for 9867 cases and 13 161 controls from 26 studies. Homozygosity for the Asp298 was associated with an increased risk of IHD (OR, 1.31; 95% CI, 1.13 to 1.51). Although there was significant heterogeneity among studies of Asp298 (P(Het)=0.0002), which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study from analysis. Homozygosity for the intron-4a allele was also significantly associated with higher risk of IHD (OR, 1.34; 95% CI, 1.03 to 1.75). However, no significant association was found with the -786C allele (OR, 1.06; 95% CI, 0.89, 1.25). CONCLUSIONS: Individuals homozygous for the Asp298 and intron-4a alleles of eNOS are at moderately increased risk of IHD. These findings support the proposal that common genetic variations in the eNOS gene contribute to atherosclerosis susceptibility, presumably by effects on endothelial NO availability.

Adult↗
PubMed1993

Simple sequence repeat polymorphism within the p53 gene.

This report describes a new polymorphism, in intron 3 of the p53 gene, which consists of a single repeat of 16 nucleotides, absent in the published wild-type p53 gene sequence. In the Caucasian population tested (n = 82), 28% of individuals were heterozygotes for this polymorphism. Using PCR-based analysis, we were able to demonstrate p53 allelic losses in three of six breast tumors from heterozygote patients tested.

Base Sequence↗
PubMed2002

Association of calpain-10 gene with microvascular function.

AIMS/HYPOTHESIS: Genotype could influence vascular function. In some populations, Calpain 10 gene polymorphisms increase susceptibility to diabetes or insulin resistance. Alterations in microvascular function could contribute to insulin resistance. This study investigated whether polymorphisms in the Calpain-10 gene influence microvascular function. METHODS: Skin maximum microvascular hyperaemia to local heating on the dorsum of the foot (30 min at 43 degrees C) was measured by Laser Doppler Fluximetry in 37 healthy volunteers. All were normoglycaemic according to World Health Organisation criteria, normotensive and not on any medication. Four polymorphisms in the calpain-10 gene were typed: SNP-44, SNP-43, SNP-19, SNP-63. The SNP common to all the described high risk haplotypes is the G-allele at SNP-43. This intron 3 polymorphism appears to influence gene expression. Microvascular function was examined in relation to polymorphisms at this site alone as well as the effects of the known extended high risk haplotypes using the SNP's above. RESULTS: Maximum microvascular hyperaemia was increased in the 21 subjects with G/G genotypes at SNP-43 compared to the combined group of subjects ( G/ A genotype at SNP-43 ( n=12) + A/ A genotype at SNP-43 ( n=4)), and the minimum microvascular resistance was reduced 49.4 (39.6-94.2) vs 67.5 (39.1-107.3) mmHg/V, p=0.007). Haplotype analysis of the hyperaemic response revealed no significant differences between haplotypes. The two groups did not differ in terms of anthropometric measures, blood pressure, insulin resistance or glucose. CONCLUSIONS/INTERPRETATION: The polymorphism that confers susceptibility to Type II (non-insulin-dependent) diabetes mellitus in some populations is associated in United Kingdom Caucasians with enhanced microvascular function in the presence of normoglycaemia.

Adult↗
PubMed1996

Genomic organization of human MXI1, a putative tumor suppressor gene.

MXI1, a member of the MYC family of transcription factors, is thought to negatively regulate MYC function and may therefore be a potential tumor suppressor gene. Using detailed restriction mapping and partial DNA sequencing analysis, we have determined the genomic organization of the human MXI1 gene to facilitate a search for mutations that affect MXI1 function. The gene spans a region of approximately 60 kb on chromosome 10q24-q25 and comprises six exons. The correspondence of these exons to previously identified Mxi1 functional domains suggests that alternatively spliced transcripts may regulate Mxi1 functional activity. The presence of a cryptic ATG start codon in exon 2 suggests that a functional protein missing the SIN3-interacting domain (exon 1) may be generated by alternative splicing. Finally, we have identified two polymorphic regions within the MXI1 locus: a polymorphic CA repeat in the third intron and an AAAAC polymorphism in the noncoding region of exon 6. These findings will facilitate the analysis of tumors for the presence of inactivating mutations in MXI1 coding and regulatory sequences.

Alternative Splicing↗
PubMed2004

The human T locus and spina bifida risk.

The transcription factor T is essential for mesoderm formation and axial development during embryogenesis. Embryonic genotype for a single-nucleotide polymorphism in intron 7 of T ( TIVS7 T/C) has been associated with the risk of spina bifida in some but not all studies. We developed a novel genotyping assay for the TIVS7 polymorphism using heteroduplex generator methodology. This assay was used to genotype spina bifida case-parent trios and the resulting data were analyzed using the transmission disequilibrium test and log-linear analyses. Analyses of these data demonstrated that heterozygous parents transmit the TIVS7-C allele to their offspring with spina bifida significantly more frequently than expected under the assumption of Mendelian inheritance (63 vs 50%, P=0.02). Moreover, these analyses suggest that the TIVS7-C allele acts in a dominant fashion, such that individuals carrying one or more copies of this allele have a 1.6-fold increased risk of spina bifida compared with individuals with zero copies. In silico analysis of the sequence surrounding this polymorphism revealed a potential target site for olfactory neuron-specific factor-1, a transcription factor expressed in the neural tube during development, spanning the polymorphic site. Several other putative, developmentally important and/or environmentally responsive transcription factor-binding sites were also identified close to the TIVS7 polymorphism. The TIVS7 polymorphism or a variant that is in linkage disequilibrium with the TIVS7 polymorphism may, therefore, play a role in T gene expression and influence the risk of spina bifida.

Alleles↗
PubMed2001

A screen for mutations in human homologues of mice exencephaly genes Tfap2alpha and Msx2 in patients with neural tube defects.

BACKGROUND: Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing neural tube. METHODS: A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRalpha, and PAX1 already shown to be related to NTD. RESULTS: Two TFAP2alpha point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57-5.39). CONCLUSIONS: Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases.

Alleles↗
PubMed2006

Sequence variation in the soluble epoxide hydrolase gene and subclinical coronary atherosclerosis: interaction with cigarette smoking.

Soluble epoxide hydrolase (EPHX2) catalyses the degradation of the vasoactive and anti-inflammatory epoxyeicosatrienoic acids and may play a role in the pathophysiology of atherosclerosis. 1337 African-Americans and 1645 Whites from the CARDIA study were genotyped for 22 and 15 EPHX2 single nucleotide polymorphisms (SNPs), respectively, to examine the associations of common EPHX2 haplotypes and genotypes with presence of coronary artery calcified plaque (CAC). The potential influence of cigarette smoking, which increases EPHX2 gene expression, on these associations was also assessed. In African-Americans, a common haplotype uniquely tagged by the R287Q polymorphism was associated with significantly greater risk for CAC (OR=1.7; 95% CI=1.04-3.0). In Whites, a common haplotype uniquely tagged by a polymorphism in Intron 11 of the gene was associated with significantly greater risk for CAC (OR=1.3; 95% CI=1.02-1.6). These haplotype-tagging polymorphisms also showed significant associations with CAC in individual SNP analyses, and these relationships were significantly modified by smoking. This detailed investigation of the association of EPHX2 genetic variation with CAC supports EPHX2's emerging role as a risk factor for atherosclerosis, whose effects are influenced by smoking.

Adolescent↗
PubMed1999

Identification of four variants in the tryptophan hydroxylase promoter and association to behavior.

One of the most replicated findings in biological psychiatry is the observation of lower 5-hydroxyindoleacetic acid concentrations, the major metabolite of serotonin, in the brain and cerebrospinal fluid of subjects with impulsive aggression. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin, however functional variants have not been reported from the coding sequence of this gene. Therefore, we screened the human TPH promoter (TPH-P) for genetic variants which could modulate TPH gene transcription. The TPH-P (2093 nucleotides) was screened for sequence variation by SSCP analysis of 260 individuals from Finnish, Italian, American Caucasian, and American Indian populations. Four common polymorphisms were identified: -7180T>G, -7065C>T, -6526A>G, and -5806G>T (designated as nucleotides upstream of the translation start site). In the Finns, the four polymorphisms had a minor allele frequency of 0.40 and in this population linkage disequilibrium between the four loci was complete. In the other populations the minor allele frequencies ranged from 0.40 to 0.45. TPH -6526A>G genotype was determined in 167 unrelated Finnish offenders and 153 controls previously studied for the TPH IVS7+779C>A polymorphism. A significant association was observed between -6526A>G and suicidality in the offenders. TPH -6526A>G and the previously reported intron seven polymorphism, TPH IVS7+779C>A, exhibited a normalised linkage disequilibrium of 0.89 in Finns. Normalized linkage disequilibrium was reduced in other populations, being 0.49 and 0.21 in Italians and American Indians, respectively. In conclusion, four TPH-P variants were identified which can be used for haplotype-based analysis to localize functional TPH alleles influencing behavior.

Adult↗
PubMed2000

Lack of association between an ecNOS gene polymorphism and diabetic nephropathy in type 2 diabetic patients with proliferative diabetic retinopathy.

The development of diabetic nephropathy shows remarkable variation among individuals. Therefore, not only hyperglycemia but also genetic factors may contribute to the development of diabetic nephropathy. The aim of the present study was to examine the contribution of the 27-bp repeat polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase gene (ecNOS4) to the development of diabetic nephropathy. For this purpose, we analyzed this polymorphism in 167 Japanese type 2 diabetic patients with proliferative diabetic retinopathy consisting of 102 patients with diabetic nephropathy (with macroalbuminuria) and 65 patients without diabetic nephropathy (with normoalbuminuria). The genotype and allele frequencies were not significantly different between patients with diabetic nephropathy and those without diabetic nephropathy (ecNOS4 "b/b" 79.4% vs. 84.6%, ecNOS4 "b/a" 20.6% vs. 15.4%, "b" allele 89.7% vs. 92.3%, "a" allele 10.3% vs. 7.7%). We conclude that the ecNOS4 polymorphism does not contribute to the development of diabetic nephropathy.

Aged↗
PubMed2001

Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage.

BACKGROUND: Lack of endothelium-derived nitric oxide is associated with vasospasm and vascular infarction. We investigated the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding endothelial nitric oxide synthase (NOS3). METHOD: In a prospective case-control study, 105 women with idiopathic recurrent miscarriage and 91 healthy controls were investigated. We used the polymerase chain reaction to identify the different alleles of a 27 base pair tandem repeat polymorphism in intron 4 of the NOS3 gene. RESULTS: The wild type B allele was identified on 329 out of 392 chromosomes (frequency 0.84). The polymorphic A allele was present on 63 chromosomes (frequency 0.16). The genotype frequencies were as follows: 68% (B/B), 31% (A/B) and.5% (A/A). The distribution of genotype frequencies was significantly different between the study and control groups for allele A/B heterozygotes (NOS3(A/B)) (36.7 versus 23.8%, P = 0.03, OR 1.6, 95% CI 1.1--3.8). Only one individual was homozygous for the A allele (NOS3(A/A)). She was in the study group. Between women with primary and secondary recurrent miscarriages, no statistically significant difference between the distribution of NOS3(A/B) genotypes (28 versus 34%) was observed. CONCLUSIONS: These data support a role for the NOS3 gene as a genetic determinant of the risk of idiopathic recurrent miscarriage.

Abortion, Habitual↗
PubMed2007

Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Prior work has shown reduced serotonin transmission to be associated with impulsivity and behavioral problems. The current study assessed the association between ADHD and two variants of the serotonin transporter gene: the 44-bp deletion/insertion polymorphism (5-HTTLPR) and the 17 bp-repeat polymorphism in intron 2 (STin2.VNTR). We hypothesized that ADHD phenotypes associated with impulsivity would show an association with these variants. Two-hundred and ninety-three ADHD trios were genotyped and analyzed using transmission disequilibrium test (TDT) analysis and haplotype analysis. We found no association between the STin2.VNTR and ADHD, but did find preferential transmission of the S allele of the 5-HTTLPR polymorphism (chi(2) = 5.751, P = 0.016) to probands with ADHD. Haplotype analysis found the L/10 haplotype was over-transmitted (chi(2) = 6.172, P = 0.013), while L/12 was under-transmitted to probands with ADHD (chi(2) = 4.866, P = 0.027).

Alleles↗
PubMed2000

Tryptophan hydroxylase polymorphisms in suicide victims.

Both environmental and genetic factors appear to contribute to the risk for suicide. The serotonergic system has been implicated in depression, impulsivity and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Suicide has been associated with polymorphisms in intron 7 of the TPH gene. These alleles were studied in samples from 47 deceased Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment spanning the region of interest was amplified. The A218C polymorphism was visualized by restriction fragment length polymorphism (RFLP) and the A779C was sequenced. Neither A218C nor A779C appeared to be associated with suicide in this population. These results did not change when the sample was stratified by age (10-21 years, 22-31 years) or when violent suicides were selected. The complexity of the phenotype of suicide may reflect multiple biological and social etiologic factors, and poses a worthy challenge for genetic studies.

Adolescent↗