The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan

Abstract

Metabolic syndrome (MetS) is a combination of medical disorders, consisting of multiple, interrelated risk factors of metabolic origin. To investigate the associations of MetS with appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5) polymorphism variants and the joint effect of cigarette smoking and these polymorphism variants on MetS in a community-based case-control study. Metabolic syndrome was defined according to the American Heart Association and National Heart Lung Blood Institute (AHA/NHLBI) criteria. A total of 237 MetS cases and 202 subjects without MetS aged 40 or over in Taiwan were analyzed. The genotypes of LRP5-rs3736228, LEPR-rs1137100, near MC4R-rs17782313 and SH2B1-rs4788102 were analyzed by the PCR-restriction fragment length polymorphism method. A strong association of the SNP rs17782313 near MC4R gene with MetS susceptibility was found. The data indicated that the C allele of near MC4R-rs17782313 is an obvious risk factor for MetS susceptibility. The joint effects of cigarette smoking and susceptible genotypes of LRP5, LEPR, near MC4R or SH2B1 genes led to a relatively higher risk of having MetS. Using subjects with the wild-type of LRP5, LEPR, near MC4R or SH2B1 genes and without a smoking habit as a reference group, those with cigarette smoking (current and former) and more than one variant type had a 4.1-fold (95 % CI = 1.6-10.2) risk of having MetS. The genotypes of the appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5), together with a cigarette smoking habit, are important risk factors for MetS.

Impact of leptin receptor gene variants on risk of non‐alcoholic fatty liver disease and its interaction with adiponutrin gene

“…Hepatic fibrosis score was found to be higher in subjects with metabolic syndrome . In a Taiwanese Han population, lower metabolic risk was reported in those bearing the GG genotype . A Japanese study in obese children showed a significantly lower total and LDL cholesterol in subjects with GG genotype .…”

“…24 In a Taiwanese Han population, lower metabolic risk was reported in those bearing the GG genotype. 25 A Japanese study in obese children showed a significantly lower total and LDL cholesterol in subjects with GG genotype. 26 Leptin level has been shown to correlate with metabolic syndrome profile such as adipocity and insulin resistance.…”

Two novel susceptibility loci for non-small cell lung cancer map to low-density lipoprotein receptor-related protein 5

“…The reason for this discrepancy is not clear, but it may be due to the fact that a high percentage of males in China smoke cigarettes (over 90% of the males in our study were smokers, compared with less than 10% of the females). Polymorphisms of rs3736228 have a combined effect with cigarette smoking; people that smoke cigarettes (current and former smokers) with rs3736228 polymorphisms have a 4.1-fold greater (95% CI, 1.6–10.2) risk of having metabolic syndrome ( 31 ). In addition, tobacco smokers have a much greater chance of developing lung cancer ( 32 ).…”

Association of type 2 diabetes mellitus with the interaction between low‐density lipoprotein receptor‐related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults

“…In addition, LRP5 is involved in glucose and cholesterol metabolism . Several studies have found that LRP5 polymorphisms are associated with obesity and obesity‐related metabolic factors, such as dyslipidemia and body mass index (BMI) . Obesity is associated with the development of insulin resistance, linked to the pathogenesis of T2DM .…”

“…8 Several studies have found that LRP5 polymorphisms are associated with obesity and obesity-related metabolic factors, such as dyslipidemia and body mass index (BMI). [9][10][11] Obesity is associated with the development of insulin resistance, linked to the pathogenesis of T2DM. 12 The LRP5 gene is a novel member of the LDL receptor family associated with type 1 diabetes mellitus, 13 so it may be a potential T2DM susceptibility gene, but the association between LRP5 and T2DM is unclear.…”