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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.
Chin Med J (Engl) 2014; 127(13):2438-44CM

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.

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.

Authors+Show Affiliations

Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China. Email: mxiaowei@yahoo.com.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.Department of Endocrinology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24985580

Citation

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, vol. 127, no. 13, 2014, pp. 2438-44.
Feng N, Ma X, Wei X, 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. Chin Med J. 2014;127(13):2438-44.
Feng, N., Ma, X., Wei, X., Zhang, J., Dong, A., Jin, M., ... Guo, X. (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), pp. 2438-44.
Feng N, 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. Chin Med J. 2014;127(13):2438-44. PubMed PMID: 24985580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population. AU - Feng,Nan, AU - Ma,Xiaowei, AU - Wei,Xiaowei, AU - Zhang,Junqing, AU - Dong,Aimei, AU - Jin,Mengmeng, AU - Zhang,Hong, AU - Guo,Xiaohui, PY - 2014/7/3/entrez PY - 2014/7/6/pubmed PY - 2015/4/8/medline SP - 2438 EP - 44 JF - Chinese medical journal JO - Chin. Med. J. VL - 127 IS - 13 N2 - 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. 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. SN - 0366-6999 UR - https://www.unboundmedicine.com/medline/citation/24985580/Common_variants_in_PERK_JNK_BIP_and_XBP1_genes_are_associated_with_the_risk_of_prediabetes_or_diabetes_related_phenotypes_in_a_Chinese_population_ L2 - http://Insights.ovid.com/pubmed?pmid=24985580 DB - PRIME DP - Unbound Medicine ER -