Published online before print January 23, 2009, doi: 10.1161/CIRCGENETICS.108.817064
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Original Articles |
Association of Regions on Chromosomes 6 and 7 With Blood Pressure in Nigerian Families
From the Department of Preventive Medicine and Epidemiology (B.O.T., A.L., R.S.C.), Loyola University Chicago Stritch School of Medicine, Maywood, Ill; Department of Biostatistics and Epidemiology (X.Z.), Case Western Reserve University, Cleveland, Ohio; and NIH Intramural Center for Research on Genomics and Global Health (A.A.), National Human Genome Research Institute, Bethesda, Md.
Correspondence to Bamidele Tayo, PhD, Department of Preventive Medicine and Epidemiology, Loyola Medical School, 2160 South First Avenue, Maywood, IL 60153. E-mail btayo{at}lumc.edu
Received August 24, 2008; accepted November 17, 2008.
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.
Key Words: blood pressure • genes • mapping • association
CLINICAL PERSPECTIVE
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Circ Cardiovasc Genet 2009 2: 38-45.[Abstract] [Full Text] [PDF]