title: An interaction between a FNDC5 variant and obesity modulates glucose metabolism in a Chinese Han population.
abstract: BACKGROUND
  To investigate the impact of common variants of FNDC5 on type 2 diabetes and clinical traits related to glucose metabolism in a large Chinese population sample.
  
  
  METHODS
  Three tagging single nucleotide polymorphisms within the region of the FNDC5 gene were selected and genotyped in 6822 participants. Detailed clinical investigations and biochemistry measurements were carried out in all of the participants. Subjects without diabetes were classified into normal weight and overweight/obese subgroups according to body mass index (BMI).
  
  
  RESULTS
  None of the SNPs were associated with either the risk of type 2 diabetes in all of the participants or with any of the clinical quantitative traits in the controls with normal glucose regulation. Subgroup analysis showed that in controls with normal weight (BMI <25 kg/m(2)), the rs16835198 major allele G was significantly associated with fasting insulin levels, and that each additional copy of the allele resulted in a 0.0178 mU/L increment of the values (p = 0.046). Moreover, after adjusting for confounding variables, there were trends towards correlation of rs16835198 with HOMA-insulin resistance (HOMA-IR) (p = 0.057) and low-density lipoprotein cholesterol (LDL-C) levels (p = 0.083). In overweight/obese subjects (BMI ≥ 25 Kg/m(2)), we noted rs16835198 showed trends towards association with fasting insulin (p = 0.057) and HOMA-IR levels (p = 0.091), both of which declined with additional copies of the major allele G. Moreover, rs16835198 was significantly associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 0.013), and HOMA-β cell function (p = 0.028) in the overweight/obese subjects. Finally, we observed a significant interaction between BMI-rs16835198 and fasting insulin levels in the control group (p = 0.003).
  
  
  CONCLUSIONS
  Our data indicate that the effect of the common FNDC5 SNP rs16835198 on fasting insulin was significantly modified by BMI in the Chinese Han population.
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Tang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Peng
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002681:China; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D050177:Overweight; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C577593:FNDC5 protein, human; D005353:Fibronectins; D007328:Insulin