RS10757278 from 9P21 is associated with st-elevated myocardial infarction in females in population of Serbia

Aim: Myocardial infarction (MI) is the clinical complication predominately caused by coronary plaque buildup and rupture during the process of atherosclerosis. In the 9p21 locus two important risk haplotype blocks have been identified. The one that carries the risk for MI with the lead variant rs10757278 and another characterized to influence progression of the MI, with the lead variant rs518394. We have investigated association of the two genetic variants with the ST-elevated MI in the gender specific manner. We have also tested variants effect on p15 mRNA level as one of the possible mechanisms of the variants effect.Methods: The study group included 147 patients (72 females) with angiographically assessed MI, and 240 healthy controls (90 females). DNA and RNA (n¼28) where isolated from peripheral blood mono nuclear leukocytes. Genotypes for rs10757278 A/G and rs518394 C/G, and relative mRNA level for p15 were determined using commercial TaqMan® assays on 7500 ABI Real-Time PCR. Results: We have found significant association of rs10757278 GG with STelevated MI occurrence, with OR of 2.2 (CI¼1.07-4.5, p¼0.03) in females. P15 mRNA was significantly down-regulated in G allele carriers (AG+GG vs AA) by a mean factor of 0.449 (S.E. range is 0.188-1.059), p¼0.019 in the whole group. The genetic variant rs518394 was not significantly associated either with MI or p15 mRNA level. Conclusions: Genotype GG of rs10757278 is significantly associated with MI occurrence in females in Serbian population. On