A widely-expressed protein tyrosine phosphatase, SHP-2, regulates apoB secretion by insulin. We hypothesised that a variation in the SHP-2 gene, PTPN11, may interact with smoking to influence serum lipid concentrations. The study comprised 794 subjects (278 males and 516 females), aged 39-88 years, who attended a health examination in Hokkaido, Japan in 2003. Subjects were genotyped for a G/A PTPN11 polymorphism (rs2301756). The mean serum LDL cholesterol, HDL cholesterol and triglyceride levels, stratified by genotype, were compared between current and non- (never or ex-) smokers. Among the AA genotype carriers, LDL cholesterol levels were significantly decreased in current vs. non-smokers [mean ± SD, 101±34 mg/dl vs. 146±40 mg/dl; b (adjusted mean difference) = −56.0; 95% CI −102.8 to −9.3; p=0.019 after adjustment for age, sex and body mass index]. In contrast, HDL cholesterol levels were increased in current vs. non-smokers (66±5 mg/dl vs. 58±12 mg/dl; b=14.9; 95% CI 3.1 to 26.8; p=0.014 after adjustment). The interaction between a current smoking habit and the AA genotype had a significant effect on LDL and HDL cholesterol (LDL-C, p=0.039; HDL-C, p=0.020). These data suggest that cigarette smoking might alter the metabolism of cholesterol in Japanese PTPN11 AA genotype carriers.

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