Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

Abstract

The 9p21 chromosomal region has been associated with coronary artery disease (CAD) in many genome wide association studies (GWAS). To date no information exists regarding the rs1333039 SNP which showed the strongest association in the WTCCC GWAS with CAD risk in the Indian population. The present study attempts to replicate the findings in the Indian population. Genotyping for rs1333049 was done in 229 cases and 151 controls by allele-specific real-time assay. A higher frequency of the risk allele rs1333049C was seen in cases (0·60) as compared with controls (0·49), which associated with CAD risk both in univariate (OR = 1·564, 95%CI = 1·154-2·119, P = 0·003) and multivariate analysis (OR = 2·460, 95%CI = 1·139-5·314, P = 0·022). Increased frequency of the risk allele was seen in younger individuals with CAD where 40% individuals in the age group 30-55 years had the CC genotype as compared with 29 and 24·5% in the age group 56-65 years and > 65 years, respectively (CC versus GG, P = 0·045). Higher incidence of the CC genotype was seen in MI patients, but missed significance when compared with controls (OR = 1·361, 95%CI = 0·954-1·942, P = 0·084). In conclusion, the rs1333049 variant is significantly associated with CAD risk and also with age of onset in the Western Indian population. However there are differences in the haplotype structure of this SNP with the neighbouring rs10757278 SNP, these differences emphasize the importance of genotyping all risk variants at this locus which could underlie the differences in risk susceptibility to CAD across populations.

Common SNP-based haplotype analysis of the 9p21.3 gene locus as predictor coronary artery disease in Tanzanian population

“…The result of our study confirmed that the rs1333049 is significantly associated with CAD in the Tanzanian population, which is in agreement with the findings in other ethnic (7,8,13,(32)(33)(34)(35)(36)(37), although a weak association was reported in some populations (38,39). Our results showed not only the rs1333049 CC genotype, but also that the C allelic form is associated with CAD congruent with the results from some populations in Europe and Asia (7,8,13,(33)(34)(35)(36)(37) though G allelic form was associated with CAD in some populations (Cakmak et al 2015). In addition, our results also confirmed the significant associations of rs2383206, rs2383207, rs10757274 and rs10757278 located on chromosome 9p21.3 with the risk of CAD as reported in multiple populations (7,8,15,16,(40)(41)(42).…”

ANRIL rs1333049 C/G polymorphism and coronary artery disease in a North Indian population - Gender and age specific associations

“…A positive risk association in the subjects above 40 years of age was seen in the study with the mutant genotype having an OR=5.506 with a highly significant p < 0.001 (Table 2). However, Bhanushali et al (2013) reported the SNP to be robustly associated with premature or Sex and age specific associations 5 the early onset CAD which is also supported by the results of Meng et al (2008), Ellis et al (2010) and the association was supported by meta-analysis study done by Palomaki et al (2010). But in present study, no mutant in the CAD patients was found below 40 years of age in the pre-specified subgroup analysis based on age.…”

“…Only two studies report data on rs1333049 C/G and CAD risk in West and North Indian populations. (Bhanushali, et al, 2013) recruited 229 CAD patients and 136 controls from West India and revealed an association towards CAD with an OR=2.460, 95% CI=1.139-5.314 and 4 Kaur et al p=0.022). Kashyap et al (2018) in their study on North Indian population reported risk for both the allelic and genotypic frequencies.…”

Is there a correlation between -174(G/C) polymorphism of IL-6 gene and the incidence of acute myocardial infarction?

“…The current study results were also supported by a study conducted on 100 cases of CAD and 150 controls of Indo European descent from Maharashtra in Western India. They found no significant differences in the frequency of the IL-6 -174G > C genotypes between cases and controls [ 21 ].…”