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Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population
Feng Nan; Ma Xiaowei; Wei Xiaowei; Zhang Junqing; Dong Aimei; Jin Mengmeng; Zhang Hong; Guo Xiaohui
关键词Unfolded Protein Response Pathway Genes Endoplasmic Reticulum Stress Single Nucleotide Polymorphisms Prediabetes
刊名CHINESE MEDICAL JOURNAL
2014-07-05
DOI10.3760/cma.j.issn.0366-6999.20140521
127期:13页:2438-2444
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED PROTEIN RESPONSE ; BETA-CELL FUNCTION ; INSULIN-RESISTANCE ; OXIDATIVE STRESS ; ER STRESS ; GLUCOSE ; SURVIVAL ; KINASE ; HOMEOSTASIS
英文摘要

Background Prediabetes is an early stage of beta-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.

Conclusion 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.

语种英语
WOS记录号WOS:000339470600008
项目编号30771033
资助机构National Natural Science Foundation of China
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51867
专题北京大学第一临床医学院_内分泌内科
作者单位Peking Univ, Hosp 1, Dept Endocrinol, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Feng Nan,Ma Xiaowei,Wei Xiaowei,et al. Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population[J]. CHINESE MEDICAL JOURNAL,2014,127(13):2438-2444.
APA Feng Nan.,Ma Xiaowei.,Wei Xiaowei.,Zhang Junqing.,Dong Aimei.,...&Guo Xiaohui.(2014).Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population.CHINESE MEDICAL JOURNAL,127(13),2438-2444.
MLA Feng Nan,et al."Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population".CHINESE MEDICAL JOURNAL 127.13(2014):2438-2444.
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