TG haplotype in the LRP8 is associated with myocardial infarction in south Indian population

Abstract

Myocardial infarction (MI) is a complex multifactorial cardiovascular disease. India experiences a much greater burden of MI, also suggesting an experimental increase of this burden in the future. The absolute reasons for MI are context dependent and differ with different geographical settings. Several reports indicate that SNPs that are associated with certain diseases in other populations may not be associated with Indian population. It is, therefore, important to validate the association of SNPs. Low density lipoprotein receptor related protein 8 (LRP8) gene plays central role in human lipoprotein metabolism as it facilitates the clearance of bad cholesterol LDL, VLDL from plasma and is reported to be associated with MI in the western population. However, this gene has not been studied in the South Indian population. We aim to test the role of the LRP8 gene variants correlating with the lipid profile in MI patients in South Indian population. We sequenced regions of SNPs rs10788952, rs7546246, rs2297660 and rs5174 of LRP8 in 100 MI patients and 100 age-matched controls. Our result revealed a total of 4 variations. None of the SNPs were significantly associated with MI (p>0.973). Interestingly, haplotype based association analysis showed TG and CG of rs10788952 and rs7546246 significantly associated with MI (p<0.01 and p<0.00005) and in particular, haplotype TG was positively correlated with the risk of MI, as this increased the LDL and total cholesterol level in MI patients in south Indians. Our results suggest that haplotype TG is a risk factor for MI in South Indian population.