Association Between SLC30A8 rs13266634 Polymorphism and Risk of T2DM and IGR in Chinese Population: A Systematic Review and Meta-Analysis

Abstract

Introduction: Published data regarding the association between solute carrier family 30, member 8 (SLC30A8) rs13266634 polymorphism and type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) risks in Chinese population are in-consistent. The purpose of this meta-analysis was to evaluate the association between SLC30A8 rs13266634 and T2DM/IGR in a Chinese population.Material and Methods: Three English (PubMed, Embase, and Web of Science) and three Chinese databases (Wanfang, CNKI, and CBMD database) were used for searching articles from January 2005 to January 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated with the random-effect model. Trial sequential analysis was also utilized.Results: Twenty-eight case-control studies with 25,912 cases and 26,975 controls were included for SLC30A8 and T2DM. Pooled risk allele C frequency for rs13266634 was 60.6% (95%CI: 59.2–62.0%) in the T2DM group and 54.8% (95%CI: 53.2–56.4%) in the control group which had estimated OR of 1.23 (95%CI: 1.17–1.28). Individuals who carried major homozygous CC and heterozygous CT genotype were at 1.51 and 1.23 times higher risk of T2DM, respectively, than those carrying minor homozygous TT. The most appropriate genetic analysis model was the co-dominant model based on comparison of OR1, OR2 and OR3. Five articles that involved 4,627 cases and 6,166 controls were included for SLC30A8 and IGR. However, no association was found between SLC30A8 rs13266634 and IGR (C vs. T, OR = 1.13, 95%CI: 0.98–1.30, p = 0.082). TSA revealed that the pooled sample sizes of T2DM exceeded the estimated required information size but not the IGR.Conclusion: The present meta-analysis demonstrated that SLC30A8 rs13266634 was a potential risk factor for T2DM, and more studies should be performed to confirm the association between rs13266634 polymorphism and IGR.

Risk of type 2 diabetes mellitus and cardiovascular complications in KCNJ11, HHEX and SLC30A8 genetic polymorphisms carriers: A case-control study

“…Moreover, zinc is essential for the process of insulin maturation to secretion and SLC30A8 gene- located in secretory granules of insulin, plays an important role in zinc transportation to the container vesicles of insulin. After non-synonymous polymorphism in SLC30A8 rs13266634, a newly formed amino acid (arginine) affects its regular function and puts down the formation and secretion of insulin, which lowers the amount of insulin in the body as a whole [ 27 , 28 ]. From our study, we observed a strong association of rs13266634 in our population to develop T2DM ( p < 0.0001, 0.001, <0.0001, and <0.0001; aOR = 2.08, 2.08, 4.18, and 5.97, respectively in allele, dominant, recessive, and homozygote model) and a similar association was reported in several meta-analyses for Asian and European population [ 42 , 43 ].…”

“…The eighth member of solute carrier family 30 ( SLC30A8 ) or Zinc transporter 8 ( ZNT8 ), mainly expressed in beta cells of pancreatic islets, a novel ZNT family member which responsibly transports zinc into insulin-containing granules from the cytoplasm and subsequently forms insulin crystal for secretion, maturation and storage [ 27 ]. At 325 position, rs13266634 of SLC30A8 gene forms tryptophan (W) in the place of arginine (R) (Arg325Trp) after polymorphism that may be correlated with impaired glucose regulation [ 28 ]. Investigations have provided evidence of the association between SLC30A8 gene variants and the risk of T2DM and cardiovascular complications [ 28 ].…”

“…At 325 position, rs13266634 of SLC30A8 gene forms tryptophan (W) in the place of arginine (R) (Arg325Trp) after polymorphism that may be correlated with impaired glucose regulation [ 28 ]. Investigations have provided evidence of the association between SLC30A8 gene variants and the risk of T2DM and cardiovascular complications [ 28 ].…”

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

“…Finally, SLC30A8 is the only candidate gene that has been linked to human T2D in genetic studies and is therefore the most promising target for a therapeutic intervention ( Table 1). Research on ZnT8 is ongoing; since 2018, multiple studies regarding T2D susceptibility in different populations have been published, highlighting the critical role of this zinc transporter in the onset of human diseases (Ding et al, 2018;Dong et al, 2018;Li et al, 2018;Lin et al, 2018;Liu et al, 2018;Plengvidhya et al, 2018). Further studies are needed to finally verify whether increased or decreased transporter activity is linked to human T2D, and therefore whether inhibition or rather activation of the transporter is required to counteract disease development.…”

<p>Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors</p>

“…Previous studies have reported that the SLC30A8 (solute carrier family 30 member 8) rs13266634 polymorphism in the major C allele was strongly associated with the risk of T2DM. 60,61 In addition, Chang et al also reported that the SLC30A8 rs13266634 SNP was associated with age as a T2DM risk factor. 196 SLC30A8 is expressed in pancreatic β-cells and encodes a zinc transporter.…”