ASSOCIATION OF REGIONS WITH HYPERTENSION IN NIGERIAN FAMILIES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 高血压与许多其他与心血管风险相关的特征具有相似的遗传性水平;然而，特定的易感基因位点一直难以定位。 我们进行了一项多阶段研究，将血压作为低风险西非人群的连续特征，预计环境暴露的复杂性和强度将降低。在我们早期的全基因组血压连锁研究中，在6号和7号染色体上发现了强有力的连锁证据。随后，我们对三个区域中总共3431个标签SNP进行了基因分型（即，152.68  6号染色体上165.99 Mb，0.29  20.67 Mb和104.09 Mb  199个家系的713个个体的7号染色体长度为123.06 Mb。我们使用单个SNP和相关单倍型进行了基于家族的关联分析。经过多重比较校正后，6个内含子SNP和1个基因间SNP与血压的相关性达到了名义上的统计学显著性（p < 0.05）。相关的内含子SNP包括6号染色体上的PARK 2基因中的两个; KCND 2中的两个，以及7号染色体上的C7 orf 58和HDAC 9基因中的一个。基因间SNP位于7号染色体上的RPA 3和GLCCI 1基因之间。这些单核苷酸多态性所在的单倍型与血压的相关性比其各自的单核苷酸多态性更强。“有风险”单倍型的频率范围为14%至48%。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。

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.