Association between SLC30A8 rs13266634 Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis

Abstract

Background: Accumulating but inconsistent data about the role of rs13266634 variant of SLC30A8 in type 2 diabetes have been reported, partly due to small sample sizes and non-identical ethnicity.

Material and methods: We searched PubMed and Cochrane Library to identify eligible studies and extract data of baseline characteristics, genotype count, odds ratio (OR), and 95% confidence interval (CI). Both adjusted OR with 95% CI and genotype counts were employed to assess the association. Genotype data were further pooled to provide estimates under different genetic models and the most appropriate model was determined. Sensitivity and cumulative analysis were conducted to assure the strength of results.

Results: Fifty-five datasets of 39 studies (including 38 of 24 with genotype count) were included. Significant associations were found in allelic contrasts using adjusted ORs and raw genotype count, respectively, overall in Asian and European populations (overall: OR=1.147/1.157, 95% CI 1.114-1.181/1.135-1.180; Asian: OR=1.186/1.165, 95% CI 1.150-1.222/1.132-1.198; European: OR=1.100/1.151, 95% CI 1.049-1.153/1.120-1.183; All p=0.00), but not in African populations (African: OR=1.255/1.111, 95% CI 0.964-1.634/0.908-1.360, p=0.091/0.305). Further analysis with genotype count under different genetic models all showed that individuals with CC genotype had 33.0% and 16.5% higher risk of type 2 diabetes than those carrying TT and CT genotypes, respectively, under the most likely codominant model. Cumulative analysis indicated gradually improved precision of estimation after studies accumulated.

Conclusions: Our results suggest that rs13266634 may be an important genetic factor of type 2 diabetes risk among Asian and European but not African populations.

Figure 1

Flow diagram of study selection.

Figure 2

Stratified analysis based on ethnicity for the association between SLC30A8 polymorphism rs13266634 and type 2 diabetes risk under allelic model. (A) Using individual adjusted ORs from all original articles, (B) using individual calculated ORs from studies with detailed genotype distribution. Each study is shown by the point estimate of the odds ratio, and a horizontal line denotes the 95% confidence interval. The pooled odds ratio is represented by a diamond. The area of the grey squares reflects the weight of the study in the meta-analysis.

Figure 3

Stratified analysis based on ethnicity for the association between SLC30A8 polymorphism rs13266634 and type 2 diabetes risk under codominant genetic model. (A) CC vs. TT, (B) CC vs. CT. Each study is shown by the point estimate of the odds ratio, and a horizontal line denotes the 95% confidence interval. The pooled odds ratio is represented by a diamond. The area of the grey squares reflects the weight of the study in the meta-analysis.

Figure 4

Cumulative meta-analysis of associations between the rs13266634 variant of SLC30A8 with type 2 diabetes risk in allelic contrasts sorted by publication year. The horizontal line shows the accumulation of estimates as each study was added, and is not the estimate of a single study. (A) Using individual adjusted ORs from all original articles, (B) using individual calculated ORs from studies with detailed genotype distribution.

Figure 5

Begg’s publication bias funnel plot of the ORs for SLC30A8 mutation rs13266634 and the standard error of natural logarithm of the ORs for the included studies. Circles represent individual studies and a dash line indicates 95% confidence interval. (A) Using individual adjusted ORs from all original articles, (B) using individual calculated ORs from studies with detailed genotype distribution.