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SLC4A5 gene polymorphisms are associated with cardiovascular and metabolic phenotypes in the HERITAGE Family study
Author(s) -
Stuetz Adrian M,
Rao D.C.,
Rice Treva,
Bouchard Claude,
Rankinen Tuomo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a571-b
Subject(s) - haplotype , single nucleotide polymorphism , phenotype , genetics , biology , genotype , medicine , gene
The sodium bicarbonate cotransporter gene (SLC4A5) has been associated with cardiovascular phenotypes in two large studies. We investigated the associations between SLC4A5 polymorphisms and cardiovascular and metabolic traits in the HERITAGE Family Study. Five single nucleotide polymorphisms (SNPs) rs1667627, rs828853 , rs7571842, rs2034454 and rs6731545 were analyzed in 276 Black and 503 White healthy, sedentary subjects. In Whites, haplotypes 2 and 5, defined by SNPs rs7571842, rs2034454, and rs6731545, were associated with resting and submaximal exercise systolic blood pressure and pulse pressure (0.048>p>0.0003). In addition, oxygen consumption, CO 2 production and minute ventilation during submaximal exercise showed strong associations with haplotype 2 (p<0.0009). Haplotype 2 homozygotes had lower phenotype levels than subjects with other haplotypes. Haplotype 2 explained from about 1 to 3.5% of the variance in these phenotypes. Haplotype associations were confirmed in single marker analysis. No significant associations were found in Blacks. These results in the HERITAGE Family Study confirm previous studies on cardiovascular phenotypes at rest and extend them to observations at submaximal exercise. A novel finding is the strong association between the SLC4A5 genotypes and submaximal exercise metabolic traits. Supported by NHLBI HL045670