title: Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population.
abstract: BACKGROUND
  Prediabetes is an early stage of β-cell dysfunction presenting as insulin resistance. Evidences suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis of type 2 diabetes mellitus and prediabetes. In a Chinese population with prediabetes, we investigated single nucleotide polymorphisms (SNPs) in the genes of PERK, JNK, XBP1, BIP and CHOP which encode molecular proteins involved in ER stress pathways.
  
  
  METHODS
  Nine SNPs at the PERK, JNK, XBP1, BIP and CHOP loci were genotyped by mass spectrometry in 1 448 unrelated individuals. By using a 75 g oral glucose tolerance test (OGTT), 828 subjects were diagnosed as prediabetes and 620 subjects aged 55 years and over as normal controls based on WHO diagnostic criteria (1999) for diabetes mellitus.
  
  
  RESULTS
  The allele C of SNP rs867529 at PERK locus was a risk factor for prediabetes, with the carriers of C allele genotype at a higher risk of prediabetes compared to non-carriers (OR = 1.279, 95% CI: 1.013-1.614, P = 0.039, after adjustment for age, sex and body mass index (BMI). The SNPs rs6750998 at PERK locus was associated with homeostasis model assessments of insulin resistance (HOMA-IR) (P = 0.019), and rs17037621 with BMI (P = 0.044). The allele G of SNP rs10986663 in BIP gene was associated with a decreased risk of prediabetes (OR = 0.699, 95% CI: 0.539-0.907, P = 0.007). The SNP rs2076431 in JNK gene was associated with fasting plasma glucose levels (P = 0.006) and waist-hip ratios (P = 0.019). The SNP rs2239815 in XBP1 gene was associated with 2-hour plasma glucose levels after 75 g oral glucose load (P = 0.048) in the observed population.
  
  
  CONCLUSIONS
  Common variants at PERK and BIP loci contributed to the risk of prediabetes, and the genetic variations in JNK and XBP1 genes are associated with diabetes-related clinical parameters in this Chinese population.
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China. Email: mxiaowei@yahoo.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Dong
authors.affiliation: Department of Endocrinology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Guo
mesh_terms: D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011236:Prediabetic State / Q000235:genetics*; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase; D048670:MAP Kinase Kinase 4