ASSOCIATION OF REGIONS WITH HYPERTENSION IN NIGERIAN FAMILIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 高血压的遗传性水平与许多其他与心血管风险相关的特征相似；然而，特定的易感基因座很难定位。我们在一个低风险的西非人群中进行了一项关于血压作为一种持续特征的多阶段研究，预计环境暴露的复杂性和强度将会降低。在我们早期对该人群血压的全基因组连锁研究中，在6号和7号染色体上发现了很强的连锁证据。随后，我们在3个区域(6号染色体上的152.68 165.99 Mb，7号染色体上的0.29 20.67 Mb和104.09 123.06 Mb)对713名个体的3 431个标签SNPs进行了基因分型。我们利用个体SNP和相关的单倍型进行了基于家庭的关联分析。经多次比较校正后，6个内含子SNP和1个基因间SNP在与血压的关联方面具有名义统计学意义(p&lt；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中的2个，7号染色体上的C7orf58和HDAC9基因各1个。基因间SNP位于7号染色体上的RPA3和GLCCI1基因之间。这些SNP所在的单倍型与血压的相关性比它们各自的单个SNP更强。“高危”单倍型的频率从14%到48%不等。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会影响血压升高的易感性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypertension 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 multi-stage study of blood pressure as a continuous trait in a low-risk West African population where it was anticipated that environmental exposures would be reduced in complexity and intensity. In our earlier genome-wide linkage study for blood pressure in this population strong linkage evidence was noted on chromosomes 6 and 7. We subsequently genotyped a total of 3431 tag SNPs in three regions (viz, 152.68  165.99 Mb on chromosome 6, 0.29  20.67 Mb and 104.09  123.06 Mb on chromosome 7) in 713 individuals from 199 families. We conducted family-based association analysis using individual SNPs and associated haplotypes. After correction for multiple comparisons, six intronic SNPs and one intergenic SNP achieved nominal statistical significance (p < 0.05) for association with blood pressure. The associated intronic SNPs include two in the PARK2 gene on chromosome 6; two in the KCND2, and one 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 blood pressure than their respective single SNPs. The frequency of the "at risk" haplotypes ranged from 14% to 48%. These data provide preliminary evidence that regions on chromosomes 6 and 7 may influence susceptibility to elevations in blood pressure.