title: 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.
abstract: BACKGROUND
  Low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism. The present cohort study evaluated associations of LRP5 variants with the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population.
  
  
  METHODS
  In all, 7751 subjects aged ≥18 years without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, and 5511 with a clear disease outcome were eligible for analysis. The same questionnaire was administered and the same anthropometric and blood biochemical examinations were performed at baseline and follow-up. Association analysis was performed for five single nucleotide polymorphisms and haplotypes of LRP5.
  
  
  RESULTS
  Cox proportional hazards testing of three different genetic models found no significant association between T2DM and LRP5 after adjusting for potential risk factors (P > 0.05). However, the incidence of T2DM in subjects with LRP5 mutational genotypes was higher in the overweight/obese than normal weight population. Under the dominant model, the risk of T2DM was increased with an interaction between rs11228303 and the waist-to-height ratio adjusted for baseline age, sex, and family history of T2DM (synergy index [SI] = 4.172; 95% confidence interval [CI] 1.014-17.166)], and body mass index (SI = 3.237; 95% CI 1.102-9.509). Furthermore, the A allele of rs3758644 was related to decreased fasting plasma insulin and homeostatic model assessment of β-cell function levels, whereas the T allele of rs12363572 was related to increased high-density lipoprotein cholesterol levels in new-onset diabetes patients (P < 0.05).
  
  
  CONCLUSIONS
  The risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to β-cell function and lipid metabolism.
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Discipline of Public Health and Preventive Medicine, Center of Preventive Medicine Research and Assessment, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Guo'an
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.
authors.forename: Dongting
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Chongjian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.|Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Bingyuan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Chengyi
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Pang
authors.affiliation: Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.|Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D050177:Overweight / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012424:Rural Population / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires
chemical_list: C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5
keywords: 
  Chinese; 2型糖尿病; cohort study; interaction; low-density lipoprotein receptor-related protein 5 (LRP5); type 2 diabetes mellitus; 中国人; 交互作用; 低密度脂蛋白受体相关蛋白5; 队列研究