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Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

ABSTRACT: Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

SUBMITTER: Yang HC

PROVIDER: S-EPMC2674219 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

Yang Hsin-Chou HC Liang Yu-Jen YJ Wu Yi-Lin YL Chung Chia-Min CM Chiang Kuang-Mao KM Ho Hung-Yun HY Ting Chih-Tai CT Lin Tsung-Hsien TH Sheu Sheng-Hsiung SH Tsai Wei-Chuan WC Chen Jyh-Hong JH Leu Hsin-Bang HB Yin Wei-Hsian WH Chiu Ting-Yu TY Chen Chin-Iuan CI Fann Cathy S J CS Wu Jer-Yuarn JY Lin Teng-Nan TN Lin Shing-Jong SJ Chen Yuan-Tsong YT Chen Jaw-Wen JW Pan Wen-Harn WH

PloS one 20090507 5

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the result ...[more]

PMID: 19421330

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Project description:BACKGROUND:Pulmonary hypertension (PH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, which has been associated with a high mortality rate. The pathogenesis of PH is complex and incompletely understood, which includes both genetic and environmental factors that alter vascular structure and function. METHODS:Thus we aimed to reveal the potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes. Totally 208 individuals from Chinese Han population were enrolled in the present study, including 109 non-idiopathic PH patients and 99 healthy controls. RESULTS:The data revealed that 2 SNPs were associated with PH overall susceptibility at p?<?3×10-?4 after Bonferroni correction. The top hit was rs6557421 (p?=?4.5×10-?9), located within Nox3 gene on chromosome 6. Another SNP rs3744439 located in Tbx4 gene, also showed evidence of association with PH susceptibility (p?=?1.2×10-?6). The distribution of genotype frequencies of rs6557421 and rs3744439 have dramatic differences between PH patients and controls. Individuals with rs6557421 TT genotype had a 10.72-fold/14.20-fold increased risk to develop PH when compared with GG or GG/GT carriers in codominant or recessive model, respectively (TT versus GG: 95%CI?=?4.79-24.00; TT versus GG/GT: 95%CI?=?6.65-30.33). As for rs3744439, AG genotype only occurred in healthy controls but has not been observed in PH patients. We further validated the result by using 26 different populations from five regions around the globe, including African (AFR), American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS). In consistent with the present case-control study's results, significantly different genotype frequencies of the observed SNPs existed between PH patients and healthy individuals from all over the world. CONCLUSIONS:The results suggested that rs6557421 variant in Nox3 and rs3744439 variant in Tbx4 might have potential effect on individual susceptibility to pulmonary hypertension, which could lead to therapeutic or diagnosis approaches in PH.

Dataset Information

Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

Publications

Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

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