Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection against myocardial infarction in Europeans.

Abstract

Single-nucleotide polymorphisms within the BAT1-NFKBIL1-LTA genomic region (6p21.3) and the LGALS2 gene (22q13.1), encoding a regulator for lymphotoxin-alpha, the product of the LTA gene, have been reported to be linked with the risk of myocardial infarction in Japanese. We employed nine polymorphisms from the BAT1-NFKBIL1-LTA region and one polymorphism from the LGALS2 gene, and investigated whether such associations were also present in Europeans. The study included 3657 patients with myocardial infarction and 1211 control individuals with angiographically normal coronary arteries. Minor homozygous genotypes of polymorphisms in BAT1 (rs2239527, -23C/G), NFKBIL1 (rs2071592, -63T/A) and LTA (rs1800683, -162G/A; rs909253, 252G/A; rs1041981, Thr26Asn) were associated with moderately protective effects against myocardial infarction (P </= 0.045). The most abundant 9-marker haplotype of the BAT1-NFKBIL1-LTA region, named haplotype 1 (28% frequency in the study population), included the alleles of the five protective genotypes and was related with a significantly lower risk of myocardial infarction (OR 0.88, 95% CI 0.80-0.98; P = 0.015). Moreover, homozygosity for haplotype 1 was associated with an OR 0.72 (95% CI 0.57-0.90; P = 0.0047). Multiple logistic regression analysis revealed an independent protective effect against myocardial infarction in the homozygous carriers of haplotype 1 (adjusted OR 0.78, 95% CI 0.62-0.99; P = 0.043). A putative risk genotype of the polymorphism in the LGALS2 gene (rs7291467; 3279T/C) was not associated with myocardial infarction (OR 0.98, 95% CI 0.83-1.16; P = 0.84). Our finding that protective effects are linked with minor homozygous genotypes and haplotype 1 of the BAT1-NFKBIL1-LTA region in Europeans is opposite to the observation of associated risks in Japanese.

• Authors: Werner Koch, Petra Hoppmann, Elena Michou, Vanessa Jung, Arne Pfeufer, Jakob C Mueller, Christian Gieger, H-Erich Wichmann, Thomas Meitinger, Albert Schömig, Adnan Kastrati
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 16 Issue 15 Pg. 1821-7 (Aug 01 2007) ISSN: 0964-6906 [Print] England
• PMID: 17517687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Galectin 2
• Histocompatibility Antigens Class II
• LGALS2 protein, human
• Lymphotoxin-alpha
• NFKBIL1 protein, human
• DDX39B protein, human
• DEAD-box RNA Helicases

Topics

• Adaptor Proteins, Signal Transducing
• Aged
• Case-Control Studies
• DEAD-box RNA Helicases (genetics)
• Female
• Galectin 2 (genetics)
• Genetic Predisposition to Disease
• Genome, Human
• Genotype
• Haplotypes
• Histocompatibility Antigens Class II (genetics)
• Humans
• Lymphotoxin-alpha (genetics)
• Male
• Middle Aged
• Myocardial Infarction (ethnology, genetics)
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• White People (genetics)