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尼日利亚家庭中6号和7号染色体区域与血压的关联

Association of regions on chromosomes 6 and 7 with blood pressure in Nigerian families.

作者信息

Tayo Bamidele O, Luke Amy, Zhu Xiaofeng, Adeyemo Adebowale, Cooper Richard S

机构信息

Department of Preventive Medicine and Epidemiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.

出版信息

Circ Cardiovasc Genet. 2009 Feb;2(1):38-45. doi: 10.1161/CIRCGENETICS.108.817064. Epub 2009 Jan 23.

Abstract

BACKGROUND

Elevated blood pressure (BP) shares a level of heritability similar to many other traits related to cardiovascular risk; however, specific susceptibility loci have been difficult to localize. We conducted a multistage study of BP as a continuous trait in a low-risk West African population in which it was anticipated that environmental exposures would be reduced in complexity and intensity. In our earlier genome-wide linkage study for BP in this population, strong linkage evidence was noted on chromosomes 6 and 7.

METHODS AND RESULTS

We subsequently genotyped a total of 3431 tag single-nucleotide polymorphisms (SNPs) in 3 regions (viz, 152.68 to 165.99 Mb on chromosome 6, 0.29 to 20.67 Mb, and 104.09 to 123.06 Mb on chromosome 7) in 713 individuals from 199 families. We conducted a family-based association analysis using individual SNPs and associated haplotypes. After correction for multiple comparisons, 6 intronic and 1 intergenic SNPs achieved nominal statistical significance (P<0.05) for the association with BP. The associated intronic SNPs include 2 in the PARK2 gene on chromosome 6; 2 in the KCND2 gene, and 1 each in the C7orf58 and HDAC9 genes on chromosome 7. The intergenic SNP is located between the RPA3 and GLCCI1 genes on chromosome 7. The haplotypes on which these SNPs resided were more strongly associated with BP than their respective single SNPs. The frequency of the "at-risk" haplotypes ranged from 14% to 48%.

CONCLUSIONS

These data provide preliminary evidence that regions on chromosomes 6 and 7 may influence susceptibility to elevations in BP.

摘要

背景

血压升高与许多其他心血管风险相关性状具有相似水平的遗传度;然而,特定的易感基因座一直难以定位。我们在一个低风险的西非人群中对血压作为连续性性状进行了多阶段研究,预计该人群中环境暴露的复杂性和强度会降低。在我们早期针对该人群血压的全基因组连锁研究中,在6号和7号染色体上发现了强烈的连锁证据。

方法与结果

随后,我们在来自199个家庭的713名个体中,对3个区域(即6号染色体上152.68至165.99兆碱基、7号染色体上0.29至20.67兆碱基以及104.09至123.06兆碱基)的总共3431个标签单核苷酸多态性(SNP)进行了基因分型。我们使用单个SNP和相关单倍型进行了基于家系的关联分析。在进行多重比较校正后,6个内含子SNP和1个基因间SNP与血压的关联达到了名义统计学显著性(P<0.05)。相关的内含子SNP包括6号染色体上PARK2基因中的2个;KCND2基因中的2个,以及7号染色体上C7orf58和HDAC9基因各1个。基因间SNP位于7号染色体上RPA3和GLCCI1基因之间。这些SNP所在的单倍型与血压的关联比其各自的单个SNP更强。“风险”单倍型的频率范围为14%至48%。

结论

这些数据提供了初步证据,表明6号和7号染色体上的区域可能影响血压升高的易感性。

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