title: Interaction Between Peroxisome Proliferator Activated Receptor δ and Epithelial Membrane Protein 2 Polymorphisms Influences HDL-C Levels in the Chinese Population.
abstract: Peroxisome proliferator activated receptors (PPARs) are transcription factors involved in the regulation of key metabolic pathways. Numerous in vivo and in vitro studies have established their important roles in lipid metabolism. A few SNPs in PPAR genes have been reported to be associated with lipid levels. In this study, we aimed to investigate the interactive effects between single nucleotide polymorphisms (SNPs) in three PPAR isoforms α/δ/γ and other genetic variants across the genome on plasma high-density lipoprotein-cholesterol (HDL-C) levels. Study subjects (N = 2003) were genotyped using Illumina HumanOmniZhongHua-8 Beadchip. Fifty-three tag SNPs ± 100 kb of PPAR α, δ, and γ (r(2) < 0.2) were selected. The effect of interactions between PPAR SNPs and those across the genome on HDL-C was tested using linear regression models. One statistically significant interaction influencing HDL-C was detected between PPARδ SNP rs2267668 and epithelial membrane protein 2 (EMP2) downstream SNP rs7191411 (N = 1993, β = 0.74, adjusted P = 0.022). This interaction was successfully replicated in the meta-analysis of two additional Chinese cohorts (N = 3948, P = 0.01). The present study showed a novel SNP × SNP interaction between rs2267668 in PPARδ and rs7191411 in EMP2 that has significant impact on circulating HDL-C levels in the Singaporean Chinese population.
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: Tingjing
authors.initials: T
authors.lastname: Ke
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Dorajoo
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.|Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Duke-NUS Graduate Medical School, Singapore.
authors.forename: Woon-Puay
authors.initials: WP
authors.lastname: Koh
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore.
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: Daniel Y T
authors.initials: DY
authors.lastname: Goh
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Singapore National Eye Centre, Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Singapore National Eye Centre, Singapore Eye Research Institute, Singapore.|Academic Medicine Research Institute, Duke-NUS Graduate Medical School, National University of Singapore, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Friedlander
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: Chew-Kiat
authors.initials: CK
authors.lastname: Heng
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China / Q000208:ethnology; D008076:Cholesterol, HDL / Q000097:blood*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012846:Singapore
chemical_list: D008076:Cholesterol, HDL; C486403:EMP2 protein, human; D008562:Membrane Glycoproteins; D047494:PPAR delta
keywords: HDL-C; PPAR; SNP; genetics; interaction; lipoproteins