title: Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia.
abstract: 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 (χ(2)=22.3, p<0.001). The frequency of risk genotype CC was significantly different from the healthy controls (p<0.001, χ(2)=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.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad 45600, Pakistan.
authors.forename: Waqas
authors.initials: W
authors.lastname: Ahmed
authors.forename: Imran Saeed
authors.initials: IS
authors.lastname: Ali
authors.forename: Moeen
authors.initials: M
authors.lastname: Riaz
authors.forename: Asma
authors.initials: A
authors.lastname: Younas
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sadeque
authors.forename: Asfandyar Khan
authors.initials: AK
authors.lastname: Niazi
authors.forename: Saad Hameed
authors.initials: SH
authors.lastname: Niazi
authors.forename: Syeda Hafiza Benish
authors.initials: SH
authors.lastname: Ali
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use; D062085:RNA, Long Noncoding / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; C561518:CDKN2B antisense RNA, human; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011758:Pyrroles; D062085:RNA, Long Noncoding; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin