on January 23, 2009
Published online before print January 23, 2009, doi: 10.1161/CIRCGENETICS.108.817064
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Original Article |
Association of Regions on Chromosomes 6 and 7 With Blood Pressure in Nigerian Families
1 Loyola University Chicago Stritch School of Medicine, Maywood, IL;
2 Case Western Reserve University, Cleveland, OH;
3 NIH Intramural Center for Research on Genomics and Global Health, Bethesda, MD
4 E-mail: btayo{at}lumc.edu
Background—Elevated blood pressure 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.
Methods and Results—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 and one intergenic SNPs achieved nominal statistical significance (p < 0.05) for the 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%.
Conclusions—These data provide preliminary evidence that regions on chromosomes 6 and 7 may influence susceptibility to elevations in blood pressure.
Key Words: blood pressure • genes • mapping • association
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