Association between the TRAIL single nucleotide polymorphism rs1131580 and type 2 diabetes mellitus in a Han Chinese population

Abstract

ABSTRACT. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is expressed in different tissues and cells, including the pancreas and lymphocytes, and it can selectively induce apoptosis in tumor cells but not in most normal cells. TRAIL plays critical roles in type 1 diabetes mellitus, and is involved in type 2 diabetes mellitus (T2DM). We recently discovered the association of nonalcoholic fatty liver disease, a risk factor for T2DM, with a single nucleotide polymorphism (SNP) in the TRAIL (TNFSF10) gene at site 1595C/T (rs1131580), indicating the possible association of T2DM with this TRAIL polymorphism. The aim of this study was to investigate the relationship of the TRAIL SNP at site 1595C/T (rs1131580) with T2DM susceptibility and the biometabolic parameters of T2DM in a Han Chinese population. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype SNP rs1131580 in 292 patients with T2DM and 266 healthy controls. We found that the frequency of the CC genotype and that of the C allele of rs1131580 were significantly higher in T2DM patients than in the control group. Additionally, the triglyceride and serum creatinine levels of T2DM patients with the CC genotype were significantly higher than those of patients with the TT genotype. Thus, the CC genotype of the TRAIL SNP at 1595C/T (rs1131580) confers increased susceptible to T2DM in a Han Chinese population from Shandong Province. These data suggest that the CC genotype at this SNP is related to diabetic severity and it might be a candidate for the prognostic assessment of T2DM.

Association of the rs11196218 polymorphism in TCF7L2 with type 2 diabetes mellitus in Asian population

“…T2DM is a complex disease affected by both genetic and environmental factors ( Gujral et al, 2013 ). Many genetic association studies have suggested that several genes and specific SNPs are associated with risk of T2DM ( Nair et al, 2012 , Ng et al, 2008 , Rai et al, 2012 , Yu et al, 2013 ). In fact, TCF7L2 is considered the most influential gene in determining genetic susceptibility for T2DM in humans ( Luo et al, 2009 , Ng et al, 2008 , Qiao et al, 2012 , Wang et al, 2013 ).…”

Effect of trail C1595T variant and gene expression on the pathogenesis of non-small cell lung cancer

“…Studies have shown that the 3ʹ-UTR region of exon 5 of TRAIL plays an important role in regulation of the TRAIL gene [6,24,35]. The 3ʹ-UTR, which functions as a regulatory region at the level of protein expression, binds not only to mRNA but also to mRNA coated with RNA proteins [RBPs] and microRNAs (miRNAs), which play important roles in the regulation of translation [24,36].…”

“…The 3ʹ-UTR, which functions as a regulatory region at the level of protein expression, binds not only to mRNA but also to mRNA coated with RNA proteins [RBPs] and microRNAs (miRNAs), which play important roles in the regulation of translation [24,36]. Studies have suggested that an allelic variation which changes the level of expression of the protein in the genome of patients, particularly in the 3ʹ-UTR, plays an important role in the outcome of the disease [36].…”

“…Recent studies have expressed that the variant of TRAIL at site 1595 could affect TRAIL gene expression by changing a potential miRNA binding sequence, due to 3ʹ-UTR of TRAIL gene may bind both naked mRNA and mRNA covered RNA proteins and miRNAs by involved in gene regulation [24,36]. In order to assess the significance of our results in this way of thinking, when we analyzed the TRAIL C1595T polymorphisms and TRAIL gene expression in NSCLC patients together, we could not find a statistically significant association between C1595T variants and TRAIL gene expression levels.…”

“…Despite the fact that polymorphisms of TRAIL have been reported in various cancers such as lung cancer [6], colon cancer [12], breast cancer [13,19], gastric cancer [20], bladder cancer [21], prostate cancer [22], and renal cancer [23], in some diseases such as type 2 diabetes mellitus [24], intervertebral disc disorder [25], multiple sclerosis [26], ulcerative colitis [27], and fatty liver disease [28]. However, the role of TRAIL polymorphism in lung cancer is yet to be elucidated [29].…”