Dataset Information

Assessment of two missense polymorphisms (rs4762 and rs699) of the angiotensinogen gene and stroke.

ABSTRACT: The renin-angiotensin system has an important role in the pathogenesis of stroke. We investigated whether two missense single nucleotide polymorphisms (SNPs; rs4762, Thr207Met, T207M; and rs699, Met268Thr, M268T) of angiotensinogen (AGT; serpin peptidase inhibitor, clade A, member 8) are associated with the development and clinical phenotypes of ischemic stroke (IS) and intracerebral hemorrhage (ICH). We analyzed 197 stroke patients (120 IS and 77 ICH) and 301 control subjects. The patients were classified into subgroups in accordance to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ?6) and Modified Barthel Index (MBI, <60 and ?60). Multiple logistic regression models were used to analyze the genotype and allele distributions of each SNP. One of the missense SNPs, rs4762 (T207M) was associated with the development of ICH (P=0.038 in log-additive model and P=0.021 in allele distributions). The T allele frequency of T207M was higher in the ICH group (16.2%) compared with the control group (9.6%). The TC haplotype frequency differed significantly between the ICH and control groups (P=0.014). With regard to clinical features, T207M correlated with the NIHSS scores of the ICH patients (P=0.039 in codominant1, P=0.015 in dominant, P=0.011 in overdominant and P=0.039 in log-additive models). However, the two missense SNPs, rs4762 and rs699, were not associated with IS and its clinical features, including NIHSS and MBI scores. These data suggest that a missense SNP (rs4762, T207M) of the AGT gene may be associated with the development of ICH and contribute to the neurological functional levels of ICH patients.

SUBMITTER: Park HK

PROVIDER: S-EPMC3524280 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Assessment of two missense polymorphisms (rs4762 and rs699) of the angiotensinogen gene and stroke.

Park Hyun-Kyung HK Kim Myung-Chun MC Kim Sung-Min SM Jo Dae Jean DJ

Experimental and therapeutic medicine 20120111 1

The renin-angiotensin system has an important role in the pathogenesis of stroke. We investigated whether two missense single nucleotide polymorphisms (SNPs; rs4762, Thr207Met, T207M; and rs699, Met268Thr, M268T) of angiotensinogen (AGT; serpin peptidase inhibitor, clade A, member 8) are associated with the development and clinical phenotypes of ischemic stroke (IS) and intracerebral hemorrhage (ICH). We analyzed 197 stroke patients (120 IS and 77 ICH) and 301 control subjects. The patients were ...[more]

PMID: 23251296

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Project description:Background and purposeHypertension (HTN) is a multifactorial chronic disease that poses a significant global health burden and is associated with increased mortality rates. It often coexists with other conditions, such as cardiovascular, liver, and renal diseases, and has a strong association with diabetes mellitus. Insulin resistance and endothelial dysfunction commonly occur in individuals with both HTN and type 2 diabetes mellitus (T2DM). Genetic factors, along with environmental and pathological factors, play a role in the development of HTN. Recent studies have revealed the influence of single nucleotide polymorphisms (SNPs) in various genes on HTN. In this study, we aimed to investigate the genetic polymorphism of angiotensinogen (AGT) T174M (rs4762) and its association with HTN in diabetic patients.MethodsA total of 300 participants were enrolled in this study and divided into three groups: control, hypertensive, and hypertensive diabetic. Blood samples were collected, and predetermined biochemical parameters were assessed. Genotyping of the AGT T174M (rs4762) gene was conducted using Tetra ARMS PCR with specific primers.ResultsThe study findings revealed a significant association between AGT T174M (rs4762) genotype and HTN in diabetic patients within the Pakistani population. The C/T genotype of AGT T174M (rs4762) was found to be significant in both the hypertensive and hypertensive diabetic participants compared to the control group. This genotype was identified as a risk factor for developing HTN in both the hypertensive and hypertensive diabetic participants.ConclusionThis study demonstrates a significant association between AGT T174M (rs4762) genetic polymorphism and HTN in diabetic patients. The C/T genotype of AGT T174M (rs4762) may serve as a potential marker for identifying individuals at risk of developing HTN, specifically in the hypertensive and hypertensive diabetic populations. Further research is warranted to elucidate the underlying mechanisms and validate these findings in larger cohorts.

Project description:Variation in the angiotensinogen gene, AGT, has been associated with variation in plasma angiotensinogen levels. In addition, the T235M polymorphism in the AGT product is associated with an increased risk of essential hypertension in multiple populations, making AGT a good example of a quantitative-trait locus underlying susceptibility to a common disease. To better understand genetic variation in AGT, we sequenced a 14.4-kb genomic region spanning the entire AGT and identified 44 single-nucleotide polymorphisms (SNPs). Forty-two SNPs were observed both in 88 white and in 77 Japanese unselected subjects. Six major haplotypes accounted for most of the variation in this region, indicating less allelic complexity than in many other genomic regions. Although the two populations were found to share all of the major AGT haplotypes, there were substantial differences in haplotype frequencies. Pairwise linkage disequilibrium (LD), measured by the D', r(2), and d(2) statistics, demonstrated a general pattern of decline with increasing distance, but, as expected in a small genomic region, individual LD values were highly variable. LD between T235M and each of the other 39 SNPs was assessed in order to model the usefulness of LD to detect a disease-associated mutation. Among the Japanese subjects, 13 (33%) of the SNPs had r(2) values >0.1, whereas this statistic was substantially higher for the white subjects (occurring in 35/39 [90%]). LD between a hypertension-associated promoter mutation, A-6G, and 39 SNPs was also measured. Similar results were obtained, with 33% of the SNPs showing r(2)>0.1 in the Japanese subjects and 92% of the SNPs showing r(2)>0.1 in the white subjects. This difference, which occurs despite an overall similarity in LD patterns in the two populations, reflects a much higher frequency of the M235-associated haplotype in the white sample. These results have important implications for the usefulness of LD approaches in the mapping of genes underlying susceptibility to complex diseases.

Dataset Information

Assessment of two missense polymorphisms (rs4762 and rs699) of the angiotensinogen gene and stroke.

Publications

Assessment of two missense polymorphisms (rs4762 and rs699) of the angiotensinogen gene and stroke.

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