The association between variants on chromosome 9p21 and inflammatory biomarkers in ethnically diverse women with coronary heart disease: a pilot study.

BACKGROUND: The most consistently replicated genetic variants associated with coronary heart disease (CHD) in populations of European descent have been found on chromosome 9p21. Yet there is little known about these associations in ethnic groups of African ancestry. These disease-associated variants are located in a genomic region of unknown function. The purpose of this exploratory study was to examine the allelic frequencies and haplotype structure of single nucleotide polymorphisms (SNPs) for Black and White women with CHD. The authors also sought to explore the relationship between these genetic variants and biomarkers of inflammation.
METHODS: Using polymerase chain reaction amplification, the authors genotyped 8 SNPs in a 58-kilobase region of chromosome 9p21 in a cohort of women with CHD (n = 91). The authors examined the interethnic relationship between the SNPs and four inflammatory biomarkers (C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor-alpha) using analysis of variance (ANOVA).
RESULTS: We found considerable interethnic allelic and haplotype diversity across the 9p21 locus, with only two SNPs in perfect linkage disequilibrium (LD) in both races. A pair of high- and low-risk haplotypes was most common in White women, while about 41% of Blacks carried the risk alleles for three of the eight SNPs the authors examined. The interethnic associations between the SNP genotypes and inflammatory markers were divergent in both direction and magnitude.
CONCLUSIONS: Our results lend support for the importance of ancestry-specific allelic context when examining variants on chromosome 9p21. Additional work is needed to elucidate the genetic contribution to inflammatory biomarkers for diverse racial groups.