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
Diabetologiajournal_title
Diabetologiaauthors
Mooyaart AL,Valk EJ,van Es LA,Bruijn JA,de Heer E,Freedman BI,Dekkers OM,Baelde HJdoi
10.1007/s00125-010-1996-1subject
Has Abstractpub_date
2011-03-01 00:00:00pages
544-53issue
3eissn
0012-186Xissn
1432-0428journal_volume
54pub_type
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