OBJECTIVE: Although an increasing number of hypertension-associated genetic variants is being reported, replication of these findings in independent studies has been challenging. Several genes in a human chromosome 1q linkage region have been reported to be associated with hypertension. We examined polymorphisms in three of these genes (ATP1B1, RGS5 and SELE) in relation to hypertension and blood pressure in a cohort of African-Americans. METHODS: We genotyped 87 single nucleotide polymorphisms (SNPs) from the ATP1B1, RGS5 and SELE genes in a well characterized cohort of 968 African-Americans and performed a case-control study to identify susceptibility alleles for hypertension and blood pressure regulation. Single SNP and haplotype association testing was done under an additive genetic model with adjustment for age, sex, BMI and ancestry-by-genotype (principal components). RESULTS: A total of 12 SNPs showed nominal association with hypertension and/or blood pressure. The strongest signal for hypertension was for rs2815272 in the RGS5 gene (P = 9.3 × 10). For SBP, rs3917420 in the SELE gene (P = 9.0 × 10) and rs4657251 in the RGS5 gene (P = 9.7 × 10) were the top hits. Effect size for each of these variants was approximately 2-3 mmHg. A five-SNP haplotype in the SELE gene also showed significant association with SBP after correction for multiple testing (P < 0.01). CONCLUSION: These findings provide additional support for the genetic role of ATP1B1, RGS5 and SELE in hypertension and blood pressure regulation.
OBJECTIVE: Although an increasing number of hypertension-associated genetic variants is being reported, replication of these findings in independent studies has been challenging. Several genes in a human chromosome 1q linkage region have been reported to be associated with hypertension. We examined polymorphisms in three of these genes (ATP1B1, RGS5 and SELE) in relation to hypertension and blood pressure in a cohort of African-Americans. METHODS: We genotyped 87 single nucleotide polymorphisms (SNPs) from the ATP1B1, RGS5 and SELE genes in a well characterized cohort of 968 African-Americans and performed a case-control study to identify susceptibility alleles for hypertension and blood pressure regulation. Single SNP and haplotype association testing was done under an additive genetic model with adjustment for age, sex, BMI and ancestry-by-genotype (principal components). RESULTS: A total of 12 SNPs showed nominal association with hypertension and/or blood pressure. The strongest signal for hypertension was for rs2815272 in the RGS5 gene (P = 9.3 × 10). For SBP, rs3917420 in the SELE gene (P = 9.0 × 10) and rs4657251 in the RGS5 gene (P = 9.7 × 10) were the top hits. Effect size for each of these variants was approximately 2-3 mmHg. A five-SNP haplotype in the SELE gene also showed significant association with SBP after correction for multiple testing (P < 0.01). CONCLUSION: These findings provide additional support for the genetic role of ATP1B1, RGS5 and SELE in hypertension and blood pressure regulation.
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