title: Modification of the effect of smoking on cholesterol in Japanese carriers of a PTPN11 polymorphism.
abstract: 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.
authors.affiliation: Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. rieokada@med.nagoya-u.ac.jp.
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishio
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima