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Haplotypes encompassing the PSMA6 and KIAA0391 Gene Cluster confer risk for Myocardial Infarction
Author(s) -
Dzimiri Nduna,
Muiya Paul,
Mohamed Gamal,
Alsmadi Osama,
AlSaud Haya,
AlMohanna Futwan,
Alshahid Maie,
Meyer Brian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.573.1
Subject(s) - haplotype , single nucleotide polymorphism , genetics , genotyping , snp , biology , gene cluster , myocardial infarction , gene , bioinformatics , medicine , allele , genotype
The proteasomal alpha subunit type 6 (PSMA6) gene is a multi‐catalytic endopeptidase believed to play an important role in regulating inflammatory processes, largely contributory to cardiovascular‐related events. It constitutes part of the KIAA0391 gene, which has similarly been implicated in some cardiovascular events. However, the involvement of this gene cluster in myocardial infarction (MI) remains poorly understood. We genotyped, using molecular beacons, five single nucleotide polymorphisms (SNPs) within this gene cluster in 1135 Saudi individuals with MI and 866 MI‐free subjects. The rs4981283 denoted as 5 [O.R. (95% C.I.) = 1.16 (1.01‐1.33); p=0.035] conferred risk, while the other four SNPs, rs8008319 (1), rs7157492 (2), rs1038990 (3), and rs12878391 (4) were not associated with MI. In contrast, three haplotypes constructed from these SNPs, consisting of 1T‐2G‐3C‐4G‐5A (χ 2 =4.19; p = 0.05), 1A‐2A‐3C‐4A‐5A (χ 2 = 7.69; p = 0.010) and 1T‐2G‐3C‐4A‐5G (χ 2 = 10.39; p = 0.020) were identified as risk factors for MI. No confounding effect of gender, age, type 2 diabetes mellitus, hyperlipidaemia, hypertension or obesity was observed on the relationships of the individual SNPs with the disorder. Therefore, our study identified three haplotypes on chromosome 14q13.2 encompassing the KIAA0391 and PSMA6 genes as conferring risk for MI. The results also point to haplotyping as a more robust tool than the individual SNP genotyping in assessing the role of gene polymorphisms in disease.