中国人的踝臂指数与利钠肽系统多态性和尿钠排泄的关系。

Ankle-brachial index in relation to the natriuretic peptide system polymorphisms and urinary sodium excretion in Chinese.

机构信息

Centre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.

出版信息

Atherosclerosis. 2013 Sep;230(1):86-91. doi: 10.1016/j.atherosclerosis.2013.06.020. Epub 2013 Jul 10.

DOI:10.1016/j.atherosclerosis.2013.06.020

PMID:23958258

Abstract

OBJECTIVE

Recent studies have demonstrated that the natriuretic pepetides induce endothelial regeneration and angiogenesis after vascular injury through the autocrine or paracrine action, and might have an inhibitory effect on atherosclerosis. We therefore systematically investigated single nucleotide polymorphisms (SNPs) in the natriuretic peptide system in relation to ankle-brachial index (ABI) in a Chinese population.

METHODS

The study population was recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009. Using the SNapShot method, we first genotyped 951 subjects enrolled in 2005 for 16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected from the primary study. ABI and plasma proBNP were measured using the Omron VP-2000/1000 device and the Elecsys proBNP immunoassay, respectively.

RESULTS

Overall, the genetic associations were not significant (P ≥ 0.07). However, in the primary study, there was significant (Pint ≤ 0.045) interaction between 3 SNPs (rs6668352, rs198388, and rs198389) at the NPPA-NPPB locus and urinary sodium excretion in relation to ABI, and the rs6668352 polymorphism had the strongest association (Pint = 0.018). In the primary combined with the validation study populations, the interaction between the rs6668352 polymorphism and urinary sodium excretion in relation to ABI remained statistically significant (Pint = 0.0036). After adjustment for covariates, the rs6668352 A allele carriers, compared with GG homozygotes, had a higher ABI (mean ± standard error, 1.103 ± 0.006 vs. 1.084 ± 0.004, P = 0.009) and lower risk of peripheral arterial disease (PAD, defined as an ABI < 0.90, odds ratio 0.37, 95% confidence interval: 0.14-0.98, P = 0.04) in the subjects of high sodium intake.

CONCLUSION

The minor alleles of 3 SNPs at the NPPA-NPPB locus are associated with a lower risk of PAD, especially in the subjects of high sodium intake.

摘要

目的

最近的研究表明，利钠肽通过自分泌或旁分泌作用诱导血管损伤后的内皮再生和血管生成，并可能对动脉粥样硬化有抑制作用。因此，我们系统地研究了中国人群中利钠肽系统中单核苷酸多态性（SNP）与踝臂指数（ABI）的关系。

方法

本研究人群于 2003 年至 2009 年从上海以南 500 公里的山区招募。我们首先使用 SNapShot 方法对 2005 年入组的 951 例患者进行 16 个 SNP 的基因分型，然后对其余 1355 例患者进行 5 个从初步研究中选择的 SNP 的验证。ABI 和血浆 proBNP 分别使用 Omron VP-2000/1000 设备和 Elecsys proBNP 免疫测定法进行测量。

结果

总体而言，遗传相关性不显著（P≥0.07）。然而，在初步研究中，NPPA-NPPB 基因座上的 3 个 SNP（rs6668352、rs198388 和 rs198389）与尿钠排泄之间的相互作用与 ABI 显著相关（Pint≤0.045），而 rs6668352 多态性的相关性最强（Pint=0.018）。在初步研究联合验证研究人群中，rs6668352 多态性与尿钠排泄与 ABI 的相互作用仍然具有统计学意义（Pint=0.0036）。在调整协变量后，与 GG 纯合子相比，rs6668352A 等位基因携带者的 ABI 更高（平均值±标准误差，1.103±0.006 与 1.084±0.004，P=0.009），高钠摄入者的外周动脉疾病（PAD，定义为 ABI<0.90）风险更低（比值比 0.37，95%置信区间：0.14-0.98，P=0.04）。