Weerapan Khovidhunkit1, Supannika Charoen2, Arunrat Kiateprungvej2, Palm Chartyingcharoen3, Suwanna Muanpetch3, Wanee Plengpanich3. 1. Hormonal and Metabolic Disorders Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Medicine, Excellence Center for Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Electronic address: wkhovid@gmail.com. 2. Hormonal and Metabolic Disorders Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Hormonal and Metabolic Disorders Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Medicine, Excellence Center for Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Abstract
BACKGROUND: Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors. Few data exist on the genetics of severe hypertriglyceridemia in Asian populations. OBJECTIVE: To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia. METHODS: We identified sequence variants of LPL, APOC2, and APOA5 by sequencing exons and exon-intron junctions in 101 subjects with triglyceride levels ≥ 10 mmol/L (886 mg/dL) and compared with those of 111 normotriglyceridemic subjects. RESULTS: Six different rare variants in LPL were found in 13 patients, 2 of which were novel (1 heterozygous missense variant: p.Arg270Gly and 1 frameshift variant: p.Asp308Glyfs*3). Four previously identified heterozygous missense variants in LPL were p.Ala98Thr, p.Leu279Val, p.Leu279Arg, and p.Arg432Thr. Collectively, these rare variants were found only in the hypertriglyceridemic group but not in the control group (13% vs 0%, P < .0001). One common variant in APOA5 (p.Gly185Cys, rs2075291) was found at a higher frequency in the hypertriglyceridemic group compared with the control group (25% vs 6%, respectively, P < .0005). Altogether, rare variants in LPL or APOA5 and/or the common APOA5 p.Gly185Cys variant were found in 37% of the hypertriglyceridemic group vs 6% in the controls (P = 3.1 × 10(-8)). No rare variant in APOC2 was identified. CONCLUSIONS: Rare variants in LPL and a common variant in APOA5 were more commonly found in Thai subjects with severe hypertriglyceridemia. A common p.Gly185Cys APOA5 variant, in particular, was quite prevalent and potentially contributed to hypertriglyceridemia in this group of patients.
BACKGROUND: Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors. Few data exist on the genetics of severe hypertriglyceridemia in Asian populations. OBJECTIVE: To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia. METHODS: We identified sequence variants of LPL, APOC2, and APOA5 by sequencing exons and exon-intron junctions in 101 subjects with triglyceride levels ≥ 10 mmol/L (886 mg/dL) and compared with those of 111 normotriglyceridemic subjects. RESULTS: Six different rare variants in LPL were found in 13 patients, 2 of which were novel (1 heterozygous missense variant: p.Arg270Gly and 1 frameshift variant: p.Asp308Glyfs*3). Four previously identified heterozygous missense variants in LPL were p.Ala98Thr, p.Leu279Val, p.Leu279Arg, and p.Arg432Thr. Collectively, these rare variants were found only in the hypertriglyceridemic group but not in the control group (13% vs 0%, P < .0001). One common variant in APOA5 (p.Gly185Cys, rs2075291) was found at a higher frequency in the hypertriglyceridemic group compared with the control group (25% vs 6%, respectively, P < .0005). Altogether, rare variants in LPL or APOA5 and/or the common APOA5 p.Gly185Cys variant were found in 37% of the hypertriglyceridemic group vs 6% in the controls (P = 3.1 × 10(-8)). No rare variant in APOC2 was identified. CONCLUSIONS: Rare variants in LPL and a common variant in APOA5 were more commonly found in Thai subjects with severe hypertriglyceridemia. A common p.Gly185Cys APOA5 variant, in particular, was quite prevalent and potentially contributed to hypertriglyceridemia in this group of patients.
Authors: Chan Joo Lee; Chi Yoon Oum; Yunbeom Lee; Sungha Park; Seok Min Kang; Donghoon Choi; Yangsoo Jang; Ji Hyun Lee; Sang Hak Lee Journal: Yonsei Med J Date: 2018-01 Impact factor: 2.759