Abstract 3565: Positional Candidate Genes for Hypertension Susceptibility in a Region of Linkage on Chromosome 2q in Two Ethnic Groups.
The goal of this study was to narrow a region of chromosome 2q with significant evidence of linkage in African-Americans (LOD=4.34 at 243 cM), and to identify potential underlying candidate hypertension susceptibility genes. We genotyped 1,640 African-Americans in 559 sibships (72% hypertensive) and 1,616 Mexican-Americans in 412 sibships (43% hypertensive) for 82 polymorphic sites in 12 positional candidate genes selected for their potential role in blood pressure regulation. Mean age of genotyped individuals was 58 years for African-Americans and 55 years for Mexican-Americans. The rs2396777 SNP in the G protein-coupled receptor 55 (GPR55) gene was most strongly associated with hypertension status in both samples (p=0.0136 in African-Americans and p=0.0019 in Mexican-Americans). GPR55 encodes a cannabinoid receptor expressed in some vascular beds. Three-SNP haplotype sliding window analyses implicated the serotonin 5-hydroxytryptamine 2B receptor (HTR2B) gene as containing variation influencing susceptibility to hypertension in both African-Americans (p=0.0091) and Mexican-Americans (p=0.0451). These results suggest the presence of genetic variation on chromosome 2q, most likely between the SLC19A3 and GPR66 genes, that acts to modify risk of hypertension.