ASSOCIATION OF REGIONS WITH HYPERTENSION IN NIGERIAN FAMILIES

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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.