Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

BACKGROUND The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUMO4) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. METHODS We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUMO4, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. RESULTS Risk alleles at three SNPs in ADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUMO4 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUMO4 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P = 0.013). CONCLUSIONS SNPs in ADIPOR1 and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.