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Meta-Analysis
. 2019 Oct;6(10):1996-2013.
doi: 10.1002/acn3.50892. Epub 2019 Sep 26.

Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis

Yating Zhao  1 , Ruixia Zhu  1 , Danni Wang  2 , Xu Liu  1
Affiliations
Meta-Analysis

Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis

Yating Zhao et al. Ann Clin Transl Neurol. 2019 Oct.

Abstract

Objective: Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk.

Methods: Relevant published studies examining the relationship between all genetic polymorphisms and DN were obtained based on a designed search strategy up to 28 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess overall pooled effects of genetic models as well as in subgroup analyses. Sensitive analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results.

Results: We conducted a systematic review of a total of 1256 articles, and then 106 publications reporting on 136 polymorphisms of 76 genes were extracted. We performed 107 meta-analyses on 36 studies involving 12,221 subjects to derive pooled effect estimates for eight polymorphisms. We identified that ACE I>D, MTHFR 1298A/C, GPx-1 rs1050450, and CAT -262C/T were associated with DN, while MTHFR C677T, GSTM1, GSTT1, and IL-10 -1082G/A were not. Sensitivity analysis, funnel plot, and Egger's test displayed robust results. Furthermore, the results of TSA indicated sufficient sample size in studies of ACE, GPx-1, GSTM1, and IL-10 polymorphisms.

Interpretation: Our study assessed the association between ACE I>D, MTHFR C677T, MTHFR 1298A/C, GPx-1 rs1050450, CAT -262C/T, GSTM1, GSTT1, and IL-10 -1082G/A polymorphisms and DN risk. We hope that the data in our research study are used to study DN genetics.

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Conflict of interest statement

The authors declare no financial or other conflicts of interests.

Figures

Figure 1
Figure 1
Flow diagram of the study selection process.
Figure 2
Figure 2
Forests for ACE I>D polymorphism and DN risk. (A) allele model (D vs. I); (B) homozygous model (DD vs. II). DN, diabetic neuropathy.
Figure 3
Figure 3
Forests for MTHFR C677T polymorphism and DN risk. (A) allele model (T vs. C); (B) recessive model (TT vs. TC + CC); (C) dominant model (TC + TT vs. CC); (D) homozygous model (TT vs. CC); (E) heterozygous model (TC vs. CC). DN, diabetic neuropathy.
Figure 4
Figure 4
Forests for MTHFR 1298A/C polymorphism and DN risk. (A) dominant model (CC + AC vs. AA); (B) heterozygous model (AC vs. AA). DN, diabetic neuropathy.
Figure 5
Figure 5
Forests for GPx‐1 rs1050450 polymorphism and DN risk. (A) allele model (T vs. C); (B) dominant model (TT + CT vs. CC); (C) homozygous model (TT vs. CC); (D) heterozygous model (CT vs. CC). DN, diabetic neuropathy.
Figure 6
Figure 6
Forests for CAT‐262C/T polymorphism and DN risk. (A) allele model (T vs. C); (B) recessive model (TT vs. CT + CC); (C) homozygous model (TT vs. CC). DN, diabetic neuropathy.
Figure 7
Figure 7
Forest for GSTM1 null/present polymorphism and DN risk. DN, diabetic neuropathy.
Figure 8
Figure 8
Forest for GSTT1 null/present polymorphism and DN risk. DN, diabetic neuropathy.
Figure 9
Figure 9
Forests for IL‐10 ‐1082G/A polymorphism and DN risk. (A) allele model (G vs. A); (B) recessive model (AA vs. AG + GG); (C) dominant model (AA + AG vs. GG); (D) homozygous model (AA vs. GG); (E) heterozygous model (AG vs. GG). DN, diabetic neuropathy.
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References

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