title: MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is among the leading public health problems in Japan, and glycated hemoglobin (HbA1c) can be used to screen the population for T2D. Gene polymorphisms, known to be associated with obesity, may predispose individuals to T2D. Rs17782313 the melanocortin 4 receptor (MC4R) has shown one of the strongest associations with body mass index (BMI). We conducted a study to investigate whether rs17782313 (TT versus TC + CC) was associated with HbA1c.
  
  
  METHODS
  We conducted a cross-sectional study including 1142 Japanese adults (446 men: 64.9 ± 14.4 years and 696 women: 66.7 ± 12.3 years). MC4R rs17782313 was genotyped using fast real-time polymerase chain reaction.
  
  
  RESULTS
  TC + CC genotype group showed significantly greater BMI (p = 0.039) and HbA1c (p = 0.001) than TT genotype group after adjustment for gender, age and, for HbA1c, BMI. Further analysis using linear regression analysis confirmed that the effect of MC4R rs17782313 on HbA1c (β = 0.08; p = 0.003) was independent of the effect age, gender, BMI, low density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and of beta cell function. This significant independent association was similarly noticed in non-obese (β = 2.82; p = 0.005) subgroups.
  
  
  CONCLUSIONS
  MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.
authors.affiliation: Department of Environmental & Preventive Medicine, Shimane University School of Medicine , Shimane , Japan .
authors.forename: Paulin Beya wa Bitadi
authors.initials: PB
authors.lastname: Mutombo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamano
authors.forename: Minoru
authors.initials: M
authors.lastname: Isomura
authors.forename: Toru
authors.initials: T
authors.lastname: Nabika
authors.forename: Kuninori
authors.initials: K
authors.lastname: Shiwaku
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*
chemical_list: D006442:Glycated Hemoglobin; D044105:Receptor, Melanocortin, Type 4; C517652:hemoglobin A1c protein, human
keywords: Inflammation; insulin resistance; insulin secretion; obesity; single nucleotide polymorphism; type 2 diabetes