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Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population.

ABSTRACT: Dysregulation of the complement system has been linked to pathogenesis of hypertension. However, whether genetic changes of complement factor H (CFH) and its related genes are associated with hypertension is unknown. We genotyped three SNPs in the CFH gene cluster that are closely linked to age-related macular degeneration, namely rs1061170 (Y402H), rs2274700 (A473A) and rs7542235 (CFHR1-3?), and tested for their associations with blood pressure and hypertension risk in a population-based cohort including 3,210 unrelated Chinese Hans (50-70 years of age) from Beijing and Shanghai. We found that rs2274700 (A473A) and rs7542235 (CFHR1-3?) were both significantly associated with diastolic blood pressure (DBP) (??=?0.632-1.431, P?0.038) and systolic blood pressure (SBP) (??=?1.567-4.445, P?0.008), and rs2274700 (A473A) was associated with hypertension risk (OR [95%CI]: 1.175 [1.005-1.373], P?=?0.048). Notably, the associations of rs2274700 (A473A) with DBP (P?=?2.1×10(-3)), SBP (P?=?8×10(-5)) and hypertension risk (P?=?7.9×10(-3)) were significant only in the individuals with low CRP levels (<2.0 mg/l), but not in those with CRP levels ?2.0 mg/l (P?0.0807) (P for interaction ?0.0467). However, no significant association between rs1061170 (Y402H) and blood pressure or hypertension risk was observed (P?0.259). In conclusion, our results suggest that genetic variations in CFH and its related genes may contribute to hypertension risk in Chinese Hans.

SUBMITTER: Gan W

PROVIDER: S-EPMC3405009 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population.

Gan Wei W Wu Johnna J Lu Ling L Xiao Xu X Huang Heng H Wang Fulong F Zhu Jingwen J Sun Liang L Liu Gang G Pan Yi Y Li Huaixing H Lin Xu X Chen Yan Y

PloS one 20120725 7

Dysregulation of the complement system has been linked to pathogenesis of hypertension. However, whether genetic changes of complement factor H (CFH) and its related genes are associated with hypertension is unknown. We genotyped three SNPs in the CFH gene cluster that are closely linked to age-related macular degeneration, namely rs1061170 (Y402H), rs2274700 (A473A) and rs7542235 (CFHR1-3Δ), and tested for their associations with blood pressure and hypertension risk in a population-based cohort ...[more]

PMID: 22848687

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Project description:ObjectiveRenalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in blood pressure (BP) regulation. We investigated the associations of renalase with BP and the risk of hypertension by examining renalase single nucleopeptide polymorphism (SNPs), serum renalase levels, and renal expression of renalase in humans.Methods① Subjects (n = 514) from the original Baoji Salt-Sensitive Study cohort were genotyped to investigate the association of renalase SNPs with longitudinal BP changes and the risk of hypertension during 14 years of follow-up. ② Two thousand three hundred and ninety two participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the association of serum renalase levels with hypertension. Renalase expression in renal biopsy specimens from 193 patients were measured by immunohistochemistry. ③ Renalase expression was compared in hypertensive vs. normotensive patients.Results① SNP rs7922058 was associated with 14-year change in systolic BP, and rs10887800, rs796945, rs1935582, rs2296545, and rs2576178 were significantly associated with 14-year change in diastolic BP while rs1935582 and rs2576178 were associated with mean arterial pressure change over 14 years. In addition, SNPs rs796945, rs1935582, and rs2576178 were significantly associated with hypertension incidence. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up after adjustment for multiple measurements. ② Hypertensive subjects had higher serum renalase levels than normotensive subjects (27.2 ± 0.4 vs. 25.1 ± 0.2 μg/mL). Serum renalase levels and BPs showed a linear correlation. In addition, serum renalase was significantly associated with the risk of hypertension [OR = 1.018 (1.006-1.030)]. ③ The expression of renalase in human renal biopsy specimens significantly decreased in hypertensive patients compared to non-hypertensive patients (0.030 ± 0.001 vs. 0.038 ± 0.004).ConclusionsThese findings indicate that renalase may play an important role in BP progression and development of hypertension.

Dataset Information

Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population.

Publications

Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population.

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