Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia

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• 作者：Waqas Ahmed^a ; Imran Saeed Ali^b ; Moeen Riaz^a ; Asma Younas^c ; Ahmed Sadeque^a ; Asfandyar Khan Niazi^d ; Saad Hameed Niazi^d ; Syeda Hafiza Benish Ali^a ; ^e ; Maleeha Azam^a ; Raheel Qamar^a ; ^d ;
• 关键词：ANRIL ; antisense non-coding RNA in the INK4 locus ; MI ; myocardial infarction ; GWAS ; genome wide association studies ; CAD ; coronary artery disease ; LD ; linkage disequilibrium ; CDKN2A ; cyclin dependant kinase inhibitor 2A ; CDKN2B ; cyclin dependant kinase in
• 刊名：Gene
• 出版年：2013
• 出版时间：25 February, 2013
• 年：2013
• 卷：515
• 期：2
• 页码：416-420
• 全文大小：174 K

文摘

Single nucleotide polymorphisms (SNPs) of non-coding RNA in the INK4 locus (ANRIL) have been found to be associated with myocardial infarction (MI). However, the effect of rs1333049:C>G in INK4 locus in familial hypercholesterolemia patients and on lipid profile of the patients has not been studied in Pakistan. We therefore investigated the association of SNP rs1333049:C>G with MI as well as familial hypercholesterolemia patients and also determined the effect of genotype on lipid levels in a northern Pakistani population. A case-control association study was performed in which 611 individuals (294 patients, 290 healthy controls and 27 patients from hypercholesterolemia families) were genotyped for rs1333049:C>G, using an Allele specific polymerase chain reaction. We found a significant association of rs1333049:C>G with MI (¦Ö² = 22.3, p < 0.001). The frequency of risk genotype CC was significantly different from the healthy controls (p < 0.001, ¦Ö² = 22.3). The risk allele C was at a higher frequency in the MI patients as compared to the controls (odds ratio [OR] = 1.55 (95 % confidence interval [CI] = 1.22-1.96), p < 0.001). The logistic regression analysis for the genotype distribution resulted in strong association of risk allele C with MI under recessive model (OR = 3.17 (95 % CI = 1.85-5.44) p < 0.001). When the data were further analyzed along the lines of gender, a significant association with both males and females was observed.

The pleiotropic role of rs1333049 was revealed further when CC genotype hypercholesterolemic individuals on statins were found to have a significantly lower TC, LDL-C and Tg levels as compared to the CG and GG individuals (p < 0.05). The current study demonstrates a strong association of the ANRIL SNP (rs1333049) with MI as well as familial hypercholesterolemia patients in a northern Pakistani population and could be used as a useful genetic marker for the screening of MI in the general Pakistani population.