Association of combined genetic variations in PPARγ, PGC-1α, and LXRα with coronary artery disease and severity in Thai population. (May 2016)

• Record Type: Journal Article
• Authors: Yongsakulchai, Pratthana; Settasatian, Chatri; Settasatian, Nongnuch; Komanasin, Nantarat; Kukongwiriyapan, Upa; Cote, Michele L.; Intharapetch, Pongsak; Senthong, Vichai
• Is Part Of: Atherosclerosis. Volume 248(2016)
• Page Start: 140
• Page End: 148
• Publication Date: 2016-05
• Subjects: PPARγ C1431T -- PGC-1α G482S -- LXRα −115G/A -- Atherosclerosis -- Severity of coronary atherosclerosis -- Coronary artery disease; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.03.005
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background: Atherosclerosis is a major cause of coronary artery disease (CAD). Peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α (LXRα), and PPARγ co-activator-1α (PGC-1α) are nuclear factors that regulate lipid metabolism and inflammation implicated in atherosclerosis. Although association of genetic variations in these nuclear factors with CAD risk has been reported, it was based on individual gene with inconsistent results among different ethnicities. We investigated the association of combined gene-polymorphisms of these nuclear factors with the risk and severity of CAD in Thai population. Methods: Hospital-based subjects, 225 CADs and 162 non-CADs, were genotyped for PPARγ C1431T, PGC-1α G482S, and LXRα −115G/A polymorphisms. Gene-polymorphisms were examined for their association with CAD risk and the severity of coronary atherosclerosis, assessed by both the number of main vessels with ≥50% stenosis and Gensini score. Results: The minor allele frequencies were 21.6% (1431T), 44.8% (482S), and 10.7% (−115A). Initially, only 482S allele revealed association with CAD risk [OR = 1.64 (95%CI: 1.01–2.66), P = 0.048] and severity [ORs for four-vessel disease = 1.23 (95%CI: 1.01–1.48), P = 0.036, and for severe atherosclerosis (score >32) = 1.76 (95%CI: 1.05–2.96), P = 0.032]. Combined two risk-genotypes, 1431T/482S and −115GG/482S, also predicted the risk of CAD [OR = 1.87 (95%CI: 1.09–3.21), P = 0.023 and OR = 1.87 (95%CI: 1.15–3.03), P = 0.012 respectively]. The combination of three risk-genotypes further increased the risk of both CAD [OR = 2.13 (95%CI: 1.12–4.06), P = 0.022] and severe coronary atherosclerosis [OR = 2.09 (95%CI 1.09–4.02), P = 0.027]. Conclusion: The combined PPARγ C1431T, PGC-1α G482S, and LXRα −115G/A polymorphisms increased the risk of CAD and predicted the severity of coronary atherosclerosis in Thais. Highlights: Genetic variants in related nuclear factors, PGC-1α G482S, PPARγ C1431T, and LXRα −115G/A, were investigated in Thais with CAD. Only 482S allele carriers were first revealed association with CAD risk and severity of coronary artery stenosis. Combined 2 risk-genotypes, of either 1431T/482S or −115G/482S, revealed stronger association with CAD risk and severity of vessel stenosis. Combined 3 risk-genotypes further increase the magnitude of CAD risk and severity of coronary artery stenosis. Combined genetic variants in PPARγ, PGC-1α, and LXRα, thus, predicts progression of coronary atherosclerosis in individual with CAD.