Genetic Variants of Retinoic Acid Receptor-Related Orphan Receptor Alpha Determine Susceptibility to Type 2 Diabetes Mellitus in Han Chinese

Abstract

Retinoic acid receptor-related orphan receptor alpha (RORA) plays a key role in the regulation of lipid and glucose metabolism and insulin expression that are implicated in the development of type 2 diabetes mellitus (T2DM). However, the effects of genetic variants in the RORA gene on the susceptibility to T2DM remain unknown. Nine tagging single-nucleotide polymorphisms (SNPs) were screened by using the SNaPshot method in 427 patients with T2DM and 408 normal controls. Association between genotypes and haplotypes derived from these SNPs with T2DM was analyzed using different genetic models. Allele and genotype frequencies at rs10851685 were significantly different between T2DM patients and control subjects (allele: p = 0.009, Odds ratios (OR) = 1.36 [95% Confidence intervals (CI) = 1.08–1.72]; genotype: p = 0.029). The minor allele T, at rs10851685, was potentially associated with an increased risk of T2DM in the dominant model, displaying OR of 1.38 (95% CI: 1.04–1.82, p = 0.025) in subjects with genotypes TA+TT vs. AA. In haplotype analysis, we observed that haplotypes GGTGTAACT, GGTGTAACC, and GATATAACT were significantly associated with increased risk of T2DM, while haplotypes GATGAAGTT, AGTGAAGTT, and AATGAAATT were protective against T2DM. These data suggest that the genetic variation in RORA might determine a Chinese Han individual’s susceptibility to T2DM.

Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms

“…Development of the high-throughput single nucleotide polymorphism (SNP) genotyping technology and completion of the HapMap project enabled the implementation of genome-wide association studies (GWAS) [ 7 ] and since 2007 they have become the leading tool for the identification of several T2D susceptibility loci [ 2 , 8 ]. Recent GWAS, initially performed in Caucasians and then in non-European populations, and meta-analyses of these studies, have increased the total number of the identified variants with possible association to over 88 variants, including and further confirming some variants that were previously identified by the linkage and candidate gene studies [ 9 , 10 ]. However, additional variants are likely to be discovered since the identified associations explain only about 10% of the heritability of the disease [ 2 , 4 , 8 ].…”

Association Mapping Approach into Type 2 Diabetes Using Biomarkers and Clinical Data

“…RORα gene has known to play an important role in the regulation of lipid and glucose metabolism and insulin expression that are involved in the development of T2D. Researchers in [24] suggested that the genetic variation in RORα gene might be an indication to the individual's susceptibility to T2D. This indicates that the effect of rs10519107 to the susceptibly to T2D could show risk association if it is investigated in another ethnicity populations.…”

Differential gene expression profiles in peripheral blood in Northeast Chinese Han people with acute myocardial infarction

“…The RORA gene is considered a predisposing gene for diabetes in Mexican Americans ( Hayes et al , 2007 ). Furthermore, mutation of an individual base in this gene is positively correlated with incidence of diabetes in the Chinese population ( Zhang et al , 2016 ). The protein encoded by the FDFT1 gene is the first enzyme in cholesterol biosynthesis, and studies have found that this gene can affect blood lipids, blood sugar, and inflammation, thus participating in obesity-related coronary heart disease, diabetes, and coronary artery calcification ( Ding et al , 2015 ).…”