HGM2002 Poster Abstracts: 7. Medical Genomics
POSTER NO: 380
Pathogenic mutations of lipoprotein lipase gene in Chinese patients with hypertriglyceridemic type 2 diabetes
2Tao Yang, 3M.W. Tsang, 1C.W. Lam, 1Y.S. Chan, 1M.K. Poon, 2S.Z. Huang, 1C.P. Pang
Elevated plasma triglyceride and nonesterified fatty acid may cause insulin resistance, an important risk fact for type 2 diabetes. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. To investigate the role of LPL gene on Chinese patients with hypertriglyceridemic type 2 diabetes, 277 patients with type 2 diabetes and 241 healthy control subjects were recruited and screened for sequence changes in LPL gene with PCR, SSCP, restriction analysis and direct DNA sequencing. Four missense mutations, Ala71Thr, Val181Ile, Gly188Glu and Glu242Lys, 1 nonsense mutation Ser447Ter, and 5 silent mutations or polymorphisms were identified. Ser447Ter was found in both patients and controls with no significant difference in the frequencies. The four missense mutations led to reduced LPL mass and enzyme activities in post-heparin plasma and in in vitro expression.
These results indicated that the 4 missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. Based on our study and published data, a putative pathogenic pathway was suggested: LPL enzyme deficiency causes elevated plasma triglyceride level and subsequent insulin resistance; Both increased free fatty acids and insulin resistance promote the gluconeogenesis and hyperglycaemia, a 'vicious circle' to progressively develop to type 2 diabetes.
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