SNPs at the 3' end of the angiotensinogen gene define two haplotypes associated with the common 235Met variant.
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ABSTRACT:
SUBMITTER: Plummer S
PROVIDER: S-EPMC379180 | biostudies-literature | 2002 Aug
REPOSITORIES: biostudies-literature
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SNPs at the 3' end of the angiotensinogen gene define two haplotypes associated with the common 235Met variant.
Plummer S S Morgan L L Kalsheker N N
American journal of human genetics 20020801 2
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Project description:BackgroundAngiotensinogen (AGT) enzyme comprises a vital module of RAAS system that effectively controls the blood pressure and related cardiovascular functions. Ample association studies have reported the importance of AGT variants in cardiovascular and non-cardiovascular adversities. But lately, owing to the complexity of the many anomalies, the haplotype based examination of genetic variation that facilitates the identification of polymorphic sites which are located in the vicinity of the causative polymorphic site, gets greater appreciation.MethodsIn the present study, we have done genotype and haplotype analysis of AGT gene in reference to hypertension to confirm the association of the two in an Indian population. To accomplish this, we performed candidate SNPs analysis and construct possible haplotypes across the AGT promoter and gene region in 414 subjects (256 Hypertensive cases and 158 controls).ResultsWe found four SNPs (rs11568020: A-152G and rs5050: A-20C in promoter; rs4762 and rs699 in exon2) and 3 haplotypes (H4, H7 and H8) that showed a stronger positive association with hypertension. The haplotype H2 was showing protective association with hypertension.ConclusionThe results of the present study confirmed and reestablished the role of AGT gene variants and their haplotypes in the causation of hypertension in Indian population and showed that haplotypes can provide stronger evidence of association.
| S-EPMC5371191 | biostudies-literature
Project description:IntroductionThe plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population.MethodsNine polymorphisms in AGT gene were genotyped, and plasma AGT level was determined by enzyme-linked immunosorbent assay.ResultsDifferences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 ± 8.3 versus TG + GG = 21.6 ± 8.8 μg/mL; P = 0.008 and C3389T (T174M), CC = 25.8 ± 9.9 versus TC + TT = 20.5 ± 5.4 μg/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (-5.1 μg/mL [95% confidence interval: -8.6 to -1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 μg/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in χ = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure.ConclusionsTwo polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population.
| S-EPMC3203016 | biostudies-literature
Project description:The heritability of high-density lipoprotein cholesterol (HDL-C) level is estimated at approximately 50%. Recent genome-wide association studies have identified genes involved in regulation of high-density lipoprotein cholesterol (HDL-C) levels. The precise genetic profile determining heritability of HDL-C however are far from complete and there is substantial room for further characterization of genetic profiles influencing blood lipid levels. Here we report an association study comparing the distribution of 139 SNPs from more than 30 genes between groups that represent extreme ends of HDL-C distribution. We genotyped 704 individuals that were selected from Genome Database of Latvian Population. 10 SNPs from CETP gene showed convincing association with low HDL-C levels (rs1800775, rs3764261, rs173539, rs9939224, rs711752, rs708272, rs7203984, rs7205804, rs11076175 and rs9929488) while 34 SNPs from 10 genes were nominally associated (p<0.05) with HDL-C levels. We have also identified haplotypes from CETP with distinct effects on determination of HDL-C levels. Our conclusion: So far the SNPs in CETP gene are identified as the most common genetic factor influencing HDL-C levels in the representative sample from Latvian population.
| S-EPMC3652817 | biostudies-literature
Project description:BACKGROUND:T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE:To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS:We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V(2), and V(5) on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS:We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION:The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.
| S-EPMC3690340 | biostudies-literature
Project description:BACKGROUND: Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. METHODS: Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. RESULTS: We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). CONCLUSION: Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.
| S-EPMC2901215 | biostudies-literature
Project description:As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case-control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF)>5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, P=0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P=0.001, OR: 1.33, 95% CI: 1.12-1.58) by χ2 test. It was identified the genotype "GG" of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; P=0.0002), while the genotype "CC" of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; P=0.0003). Furthermore, haplotype "GCT" in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher's P=0.0005; Pearson's P=0.0005), and haplotype "ATT" was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher's P=0.0013; Pearson's P=0.0013). Two single variants, the genotypes of "GG" of rs6010620 and "CC" of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998.
| S-EPMC3661361 | biostudies-literature
Project description:BackgroundIron-refractory iron deficiency anaemia (IRIDA) is a rare disorder which was linked to mutations in two genes (SLC11A2 and TMPRSS6). Common polymorphisms within these genes were associated with serum iron levels. We identified a family of Serbian origin with asymptomatic non-consanguineous parents with three of four children presenting with IRIDA not responding to oral but to intravenous iron supplementation. After excluding all known causes responsible for iron deficiency anaemia we searched for mutations in SLC11A2 and TMPRSS6 that could explain the severe anaemia in these children.Methodology/resultsWe sequenced the exons and exon-intron boundaries of SLC11A2 and TMPRSS6 in all six family members. Thereby, we found seven known and fairly common SNPs, but no new mutation. We then genotyped these seven SNPs in the population-based SAPHIR study (n = 1,726) and performed genetic association analysis on iron and ferritin levels. Only two SNPs, which were top-hits from recent GWAS on iron and ferritin, exhibited an effect on iron and ferritin levels in SAPHIR. Six SAPHIR participants carrying the same TMPRSS6 genotypes and haplotype-pairs as one anaemic son showed lower ferritin and iron levels than the average. One individual exhibiting the joint SLC11A2/TMPRSS6 profile of the anaemic son had iron and ferritin levels lying below the 5(th) percentile of the population's iron and ferritin level distribution. We then checked the genotype constellations in the Nijmegen Biomedical Study (n = 1,832), but the profile of the anaemic son did not occur in this population.ConclusionsWe cannot exclude a gene-gene interaction between SLC11A2 and TMPRSS6, but we can also not confirm it. As in this case candidate gene sequencing did not reveal causative rare mutations, the samples will be subjected to whole exome sequencing.
| S-EPMC3324414 | biostudies-literature
Project description:BackgroundMaonan nationality is a relatively conservative and isolated minority in the Southwest of China. Little is known about the association of endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations.MethodsA total of 1280 subjects of Maonan nationality and 1218 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the four LIPG SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing.ResultsSeveral SNPs were associated with high-density lipoprotein cholesterol (rs3813082, rs2000813 and rs2097055) in the both ethnic groups; total cholesterol and apolipoprotein (Apo) A1 (rs2000813) in Han nationality; and low-density lipoprotein cholesterol, ApoB, triglyceride (rs2097055) and ApoA1 (rs3819166) in Maonan minority (P < 0.0125 for all after Bonferroni correction). The commonest haplotype was rs3813082T-rs2000813C-rs2097055T-rs3819166A (Han, 44.2% and Maonan, 48.7%). The frequencies of the T-C-T-A, T-C-T-G, T-T-C-G and G-T-C-G haplotypes were different between the Maonan and Han populations (P < 0.05-0.001). The associations between haplotypes and dyslipidemia were also different in the Han and/or Maonan populations (P < 0.05-0.001).ConclusionsThe differences in serum lipid profiles between the two ethnic groups might partly be attributed to these LIPG SNPs, their haplotypes and gene-environmental interactions.Trial registrationRetrospectively registered.
| S-EPMC6325827 | biostudies-literature
Project description:Mutation within the leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a cause of autosomal dominant Parkinson's disease (PD). The purpose of this study was to determine the frequency of G2019S mutation and whether the differences in the allele and genotype distribution of six SNPs within LRRK2 gene are associated with PD in an American non-Hispanic white population. The sample included 350 sporadic PD (SPD), 225 familial PD (FPD) patients and 186 controls of the same race and ethnicity. The frequency of LRRK2 G2019S mutation in our total sample of PD (FPD and SPD) was 1.56%. The frequency of this mutation was 3.5% in the FPD and 0.3% in the SPD groups, respectively. Allele and genotype frequencies of six SNPs were compared between PD and control samples. In addition, PD groups were categorized by sporadic PD (no family history), familial PD (first degree relative with PD) and age of onset (AON, <or=50 or >or=51years). The haplotypes of the six SNPs were also constructed for association analysis. After correction for multiple comparisons, there was no association between any SNPs (allele or genotype) and PD groups. One of the haplotypes was modestly associated with the combined PD (SPD and FPD) sample. There was also no association with age at onset of PD. Our study suggests that the LRRK2 gene may be a risk factor or the cause for a very small fraction of PD in American white population.
| S-EPMC2761091 | biostudies-literature
Project description:We propose that haplotyped loci with high heterozygosity can be useful in human identification, especially within families, if recombination is very low among the sites. Three or more SNPs extending over small molecular intervals (<10 KB) can be identified in the human genome to define miniature haplotypes with moderate levels of linkage disequilibrium. Properly selected, these mini-haplotypes (or minihaps) consist of multiple haplotype lineages (alleles) that have evolved from the ancestral human haplotype but show no evidence of recurring recombination, allowing each distinct haplotype to be equated with an allele, all copies of which are essentially identical by descent. Historic recombinants, representing rare events that have drifted to common frequencies over many generations, can be identified in some cases, they do not equate to frequently recurring recombination. We have identified examples in our data collected on various projects and present eight such mini-haplotypes comprised of informative SNPs. We also discuss the ideal characteristics and advantages of minihaps for human familial identification and ancestry inference, and compare them to other types of forensic markers in use and/or that have been proposed. We expect that it is possible to carry out a systematic search and identify a useful panel of mini-haplotypes, with even better properties than the examples presented here.
| S-EPMC3476707 | biostudies-literature