Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption.
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.
Sile
Saba
S
Department of Medicine, Vanderbilt University, Nashville, Tenn 37232-0275, USA. saba.sile@vanderbilt.edu
Velez
Digna R
DR
Gillani
Niloufar B
NB
Alexander
Charles A
CA
Alexander
Charles R
CR
George
Alfred L
AL
Williams
Scott M
SM
D018118:Chloride Channels / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics*; D000075702:Nedd4 Ubiquitin Protein Ligases; D020641:Polymorphism, Single Nucleotide; D012965:Sodium Chloride / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
C440005:BSND protein, human; C489932:CLCNKA protein, human; C412733:CLCNKB protein, human; D018118:Chloride Channels; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; D012965:Sodium Chloride; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases