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The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

Abstract

Purpose

Hyperlipidaemia has been identified as a risk factor for diabetic nephropathy via exacerbation of glomerular injury through the activation of multiple signaling pathways. This study’s aim is to assess the associations between polymorphisms of genes involved in lipid metabolism, such as apolipoprotein E (ApoE), peroxisome proliferator-activated receptor γ (PPARγ), acetyl-CoA carboxylase β (ACACB), and type 2 diabetic nephropathy (T2DN).

Methods

A search of the MEDLINE and Web of Science databases was used to identify relevant studies, and allele or genotype frequencies were pooled using fixed- or random-effects models.

Results

Forty-five studies were included in this meta-analysis, consisting of 10,920 type 2 diabetic patients with nephropathy and 16,203 type 2 diabetic patients without nephropathy. The OR for ApoE ε2 versus ε3 was 1.49 (95 % CI 1.13–1.95) in T2DN. The progression of T2DN was related to the presence of the ε2 allele and ε2 carrier with ORs of 1.72 (95 % CI 1.10–2.69) and 1.78 (95 % CI 1.18–2.69), respectively. The rs1801282 C>G variant in PPARγ presented a significant association with decreased T2DN risk, both in the G allele and GC/GG genotype with ORs of 0.77 (95 % CI 0.68–0.87) and 0.79 (95 % CI 0.69–0.92), respectively. The T allele in rs2268388 within ACACB showed an increased risk for T2DN, exhibiting an OR of 1.35 (95 % CI 1.12–1.63).

Conclusions

Our meta-analysis supports that the ApoE ε2 allele and ACACB rs2268388 C>T might act as promotion factors of nephropathy in type 2 diabetes, whereas PPARγ rs1801282 C>G is a promising candidate genetic variation for reducing susceptibility to T2DN.

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Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Correspondence to Shaofa Nie or Li Liu.

Electronic supplementary material

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Begg’s funnel plots of the association between ApoE ε2/ε3/ε4 polymorphism and T2DN risk. a. ε2 vs. ε3; b. ε2 carrier vs. ε3 carrier; c. ε4 vs. ε3; d. ε4 carrier vs. ε3 carrier. The horizontal line is drawn at the pooled log OR. Diagonal lines indicate the pseudo 95 % confidence interval (CI) (TIFF 203 kb)

Begg’s funnel plots of the association between ApoE ε2/ε3/ε4 polymorphism and T2DN progression. a. ε2 vs. ε3; b. ε2 carrier vs. ε3 carrier; c. ε4 vs. ε3; d. ε4 carrier vs. ε3 carrier. The horizontal line is drawn at the pooled log OR. Diagonal lines indicate the pseudo 95 % CI (TIFF 217 kb)

Begg’s funnel plots of the association between PPARγ C>G polymorphism and T2DN risk. a. G allele vs. C allele; b. CG+GG genotype vs. CC genotype. The horizontal line is drawn at the pooled log OR. Diagonal lines indicate the pseudo 95 % CI (TIFF 166 kb)

Begg’s funnel plots of the association between ACACB C>T polymorphism and T2DN risk. a. T allele vs. C allele; b. CT+TT genotype vs. CC genotype. The horizontal line is drawn at the pooled log OR. Diagonal lines indicate the pseudo 95 % CI (TIFF 140 kb)

Sensitivity analysis for the association between ApoE ε2/ε3/ε4 polymorphism and T2DN risk. a. ε2 vs. ε3; b. ε2 carrier vs. ε3 carrier; c. ε4 vs. ε3; d. ε4 carrier vs. ε3 carrier (TIFF 389 kb)

Sensitivity analysis for the association between ApoE ε2/ε3/ε4 polymorphism and progression of T2DN. a. ε2 vs. ε3; b. ε2 carrier vs. ε3 carrier; c. ε4 vs. ε3; d. ε4 carrier vs. ε3 carrier (TIFF 193 kb)

Sensitivity analysis for the association between PPARγ C>G polymorphism and T2DN risk. a. G allele vs. C allele; b. CG+GG genotype vs. CC genotype (TIFF 309 kb)

Sensitivity analysis for the association between ACACB C>T polymorphism and T2DN risk. a. T allele vs. C allele; b. CT+TT genotype vs. CC genotype (TIFF 248 kb)

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Li, T., Shi, Y., Yin, J. et al. The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis. Int Urol Nephrol 47, 117–130 (2015). https://doi.org/10.1007/s11255-014-0843-6

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Keywords

  • Apolipoprotein E
  • Peroxisome proliferator-activated receptor γ
  • Acetyl-CoA carboxylase β
  • Polymorphism
  • Type 2 diabetes
  • Diabetic nephropathy
  • Meta-analysis