Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population
Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population
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DOI：
10.3760/cma.j.issn.0366-6999.20140521
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发表时间：
2014-07-05
影响因子：
6.1
通讯作者：
Guo Xiaohui
中科院分区：
文献类型：
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作者：
Feng Nan;Ma Xiaowei;Guo Xiaohui
背景糖尿病前期是以胰岛素抵抗为表现的β细胞功能障碍的早期阶段。有证据表明内质网应激参与了2型糖尿病及糖尿病前期的发病机制。方法应用质谱技术对1 448例糖尿病前期患者的PERK、JNK、XBP 1、BIP和CHOP基因进行单核苷酸多态性（SNPs）检测，并与正常对照组进行比较。采用75 g口服葡萄糖耐量试验（OGTT），根据1999年WHO糖尿病诊断标准，对828例糖尿病前期患者和620例55岁及以上正常对照者进行诊断。经年龄、性别和体重指数（BMI）校正后，C等位基因携带者发生糖尿病前期的风险高于非携带者（OR=1.279，95%CI：1.013-1.614，P=0.039）。PERK位点rs6750998与胰岛素抵抗稳态模型评估（HOMA-IR）相关（P=0.019），rs 17037621与BMI相关（P=0.044）。BIP基因rs 10986663等位基因G与糖尿病前期发病风险降低相关（OR=0.699，95%CI：0.539-0.907，P=0.007）。JNK基因中的SNP rs 2076431与空腹血糖水平（P=0.006）和腰臀比（P=0.019）相关。结论在中国人群中，PERK和BIP基因的共同变异与糖尿病前期的发病风险有关，JNK和XBP 1基因的遗传变异与糖尿病相关的临床指标有关。
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.