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

Pratthana Yongsakulchai; Chatri Settasatian; Nongnuch Settasatian; Nantarat Komanasin; Upa Kukongwiriyapan; Michele L Cote; Pongsak Intharapetch; Vichai Senthong

doi:10.1016/j.atherosclerosis.2016.03.005

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

Atherosclerosis. 2016 May:248:140-8. doi: 10.1016/j.atherosclerosis.2016.03.005. Epub 2016 Mar 4.

Authors

Pratthana Yongsakulchai¹, Chatri Settasatian², Nongnuch Settasatian³, Nantarat Komanasin⁴, Upa Kukongwiriyapan⁵, Michele L Cote⁶, Pongsak Intharapetch⁷, Vichai Senthong⁸

Affiliations

¹ Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
² Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: schatr@kku.ac.th.
³ Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
⁴ Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
⁵ Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
⁶ Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
⁷ Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
⁸ Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.

PMID: 27016616
DOI: 10.1016/j.atherosclerosis.2016.03.005

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.

Keywords: Atherosclerosis; Coronary artery disease; LXRα −115G/A; PGC-1α G482S; PPARγ C1431T; Severity of coronary atherosclerosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Alleles
Constriction, Pathologic / genetics
Coronary Artery Disease / ethnology
Coronary Artery Disease / genetics*
Demography
Disease Progression
Female
Genotype
Humans
Inflammation
Liver X Receptors / genetics*
Male
Middle Aged
PPAR gamma / genetics*
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
Polymorphism, Single Nucleotide*
Risk Factors
Thailand

Substances

Liver X Receptors
NR1H3 protein, human
PPAR gamma
PPARGC1A protein, human
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha