Genetic associations in diabetic nephropathy: a meta-analysis.

Abstract:

AIMS/HYPOTHESIS:This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. METHODS:PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. RESULTS:The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). CONCLUSIONS/INTERPRETATION:This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Mooyaart AL,Valk EJ,van Es LA,Bruijn JA,de Heer E,Freedman BI,Dekkers OM,Baelde HJ

doi

10.1007/s00125-010-1996-1

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

544-53

issue

3

eissn

0012-186X

issn

1432-0428

journal_volume

54

pub_type

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