The Relationship Between Polymorphisms on Chromosome 9p21 and Age of Onset of Coronary Heart Disease in Black and White Women

Abstract

Aim: Genome-wide association studies have identified variants on chromosome 9p21 that are associated with coronary heart disease (CHD). The relationship between these variants and the age of onset of CHD is less clear. The aim of this study was to examine the allelic frequencies and haplotype structure of eight single-nucleotide polymorphisms (SNPs) on chromosome 9p21 in ethnically diverse women. We also explored the relationship between 9p21 SNPs and the age of CHD onset. Results: There was considerable interethnic allelic and haplotype diversity across the 9p21 locus with only two SNPs (rs10757274 and rs4977574) in perfect linkage disequilibrium in both races, and only a small proportion of the haplotypes shared between the racial groups. With the exception of rs1333040, whites with at least one copy of the 9p21 SNP risk alleles were found to have CHD from 1.45 (rs10116277) to 4.77 (rs2383206) years earlier than those with the wild-type alleles. Blacks carrying at least one copy of the risk allele (92%) for rs1333040 had a CHD age of onset that was 6.5 years earlier than those with the wild-type alleles. Conclusions: Different variants on chromosome 9p21 may influence CHD age of onset in whites and blacks.

Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus

“…Relationships between bone disease and arterial calcification are well established, numerous studies report inverse relationships between bone mineral density (BMD) and atherosclerosis in EAs and AAs 44–46 . The 9p21 region was previously associated with coronary artery disease susceptibility in predominantly European-derived populations 36, 47, 48 . AAs with excess European ancestry in this region had higher prevalence and/or higher levels of CAC.…”

“Desert” gene (Chr9p21) variants as novel markers for coronary artery disease

“…Some studies showed a strong linkage disequilibrium (LD) between the two SNPS, rs10757278 and rs2383206 ( 26 , 34 ). Doria et al ( 26 ) showed that the G allele of rs2383206 was associated with CAD regardless of the rs10757278 allele that was present on the same haplotype, whereas the A allele of rs10757278 was protective only when it occurred together with the protective allele of rs2383206.…”

“…The association of the two SNPs rs10757278 and rs2383206 on the susceptibility locus 9p21 with CAD in multiple cohorts of European descent was demonstrated by Shen et al ( 35 ). Beckie et al ( 34 ) examined the allelic frequencies and haplotype structure of genetic variants on chromosome 9p21 in a cohort of black and white women with CHD and examined the relationship of these genetic variants with the age of onset of CHD. Few blacks as a different from whites, had the risk genotype for rs10757278 SNP, and only 12.5% of blacks had the risk genotype (GG) for rs2383206 compared with 35.2% of whites ( 34 ).…”

“…Beckie et al ( 34 ) examined the allelic frequencies and haplotype structure of genetic variants on chromosome 9p21 in a cohort of black and white women with CHD and examined the relationship of these genetic variants with the age of onset of CHD. Few blacks as a different from whites, had the risk genotype for rs10757278 SNP, and only 12.5% of blacks had the risk genotype (GG) for rs2383206 compared with 35.2% of whites ( 34 ). Another study by Beckie et al ( 36 ), comparing white women to black ones, found few blacks with the homozygous risk alleles of rs10757278-G and rs2383206-G.…”

CDKN2BAS polymorphisms are associated with coronary heart disease risk a Han Chinese population

“…This SNP was significantly associated with the risk of CHD in a Northern Indian population [23] and in African American women [24]. Genetic variation and differences in life styles among populations probably explain the population disparities in the association of this SNP and susceptibility to CHD.…”