OBJECTIVE: Differences exist among various populations with regards to hypertension prevalence, severity, progression and response to therapy. Such differences may be due to genetic or environmental factors. We characterized the genetic variation and haplotype diversity of four hypertension candidate genes (CLCNKA, CLCNKB, BSND, NEDD4L) in four different ethnic groups (Caucasian Americans, African-Americans, Han Chinese, and Mexican-Americans). METHODS: We genotyped 42 single nucleotide polymorphisms across the four genes in equal numbers of each ethnically defined population, then tested for linkage disequilibrium, computed allelic and haplotype frequencies, and compared data across the different ethnic groups. RESULTS: We identified significant genotype and allele frequency differences among ethnic groups. The strongest differences were observed between African-American and Mexican-Americans and between Caucasian and Mexican-Americans. In addition, haplotype blocks were defined for BSND, CLCNKA_B and NEDD4L in the four populations examined. Completely mismatched ('yin yang') haplotypes were also observed. We found that the number of inferred halpotypes varied gene to gene and in some instances between the populations for a given gene indicating substantial haplotype diversity. The haplotype diversity among the various ethnic populations observed in our study was greater than that reported in Perlegen database. CONCLUSIONS: Haplotype diversity in hypertension candidate genes has important implications for designing and evaluating candidate gene or genome-wide blood pressure association studies that consider these genes. Copyright 2008 S. Karger AG, Basel.
OBJECTIVE: Differences exist among various populations with regards to hypertension prevalence, severity, progression and response to therapy. Such differences may be due to genetic or environmental factors. We characterized the genetic variation and haplotype diversity of four hypertension candidate genes (CLCNKA, CLCNKB, BSND, NEDD4L) in four different ethnic groups (Caucasian Americans, African-Americans, Han Chinese, and Mexican-Americans). METHODS: We genotyped 42 single nucleotide polymorphisms across the four genes in equal numbers of each ethnically defined population, then tested for linkage disequilibrium, computed allelic and haplotype frequencies, and compared data across the different ethnic groups. RESULTS: We identified significant genotype and allele frequency differences among ethnic groups. The strongest differences were observed between African-American and Mexican-Americans and between Caucasian and Mexican-Americans. In addition, haplotype blocks were defined for BSND, CLCNKA_B and NEDD4L in the four populations examined. Completely mismatched ('yin yang') haplotypes were also observed. We found that the number of inferred halpotypes varied gene to gene and in some instances between the populations for a given gene indicating substantial haplotype diversity. The haplotype diversity among the various ethnic populations observed in our study was greater than that reported in Perlegen database. CONCLUSIONS: Haplotype diversity in hypertension candidate genes has important implications for designing and evaluating candidate gene or genome-wide blood pressure association studies that consider these genes. Copyright 2008 S. Karger AG, Basel.
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