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Abstract: The peroxisome proliferator-activated receptors (PPARs)-α,-β/δ and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation and atherosclerosis. This study examined the main effects of both single-locus and multilocus interactions among genetic variants in Chinese Han individuals to test the hypothesis that PPAR-α/δ/γ polymorphisms may contribute to the etiology of hypertriglyceridemia independently and/or through such complex interactions. We genotyped 9 single nucleotide polymorphisms for PPAR-α/δ/γ. Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu Province of China Study. 820 subjects (474 non-hypertriglyceridemia subjects, 346 hypertriglyceridemia subjects) were randomly selected. Single-locus analyses showed that after adjusted for age, sex, smoking, alcohol consumption, body mass index, waist circumference and fasting glucose, rs1800206, rs9794, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia, the OR (95% CI) were 4.43(3.08–6.37), 1.49(1.10–2.02), 1.56(1.16–2.08), 2.43(1.80–3.29), respectively. Further, generalized multifactor dimensionality reduction method analysis showed that two-to-six-locus and eight-locus models were significant (p<0.05), which indicated a potential gene–gene interaction among PPAR-α/δ/γ polymorphisms. The results suggest that PPAR-α/δ/γ polymorphisms may contribute to the risk of hypertriglyceridemia independently and/or in an interactive manner. [Copyright &y& Elsevier]