Aims Genetic basis of diabetic retinopathy (DR) is well supported by clinical evidences. More than 180 risk or protective genes have been recognized in DR pathogenesis by far. In the current study we subjected polymorphisms of genes in inflammatory pathways from independent case-control samples to systematic meta-analyses.

Methods Comprehensive electronic search strategies for PubMed, EMBASE and EBM the Cochrane Library had been established. We supplemented this search by hand searching. All case-control or cohort design studies were identified. Two reviewers independently screened out the most relevant studies and extracted the data. Uncertainties were resolved by another senior researcher. Meta-analyses were conducted with metafor package in R (v2.15.0). Tests for heterogeneity/publication bias and subgroup analysis were used to clarify the potential bias.

Results Totally 31 association studies reported 21 polymorphisms on six genes relating to inflammatory pathways. The meta-analyses showed a significant association of the T allele (T-374A) in advanced glycosylation end product-specific receptor (AGER) gene with reduced risk in developing proliferative DR (PDR; OR 0.81, 95% CI 0.7-0.94). The same results were also found for K (K469E) in intercellular adhesion molecule 1 gene (ICAM1; for PDR OR 0.68, 95% CI 0.52-0.89) and polymorphic pentanucleotide repeat (CCTTT)₁₂ within the 5’ upstream promoter region of the inducible nitric oxide synthase 2a(NOS2A) gene(for DR OR 0.69, 95% CI 0.48-0.98).

Risk variants were identified in peroxisome proliferator-activated receptor gamma gene(PPARG) and in lymphotoxin alpha gene(LTA). Missense mutation P(P12A, OR 1.53, 95% CI 1.13-2.07) in PPARG and 6(OR 1.62, 95% CI 1.05-2.49), 8(OR 1.88, 95% CI 1.07-3.31), 15(OR 2.45, 95% CI 1.43-4.19) times of the GT repeat related to LTA might considerably increase the susceptibility to DR in type 2 diabetes. In addition, allele (GT)₁₅ seem to have a strong effect (OR 3.47, 95% CI 1.79-6.71) on the development of PDR.

Conclusion Meta-analyses support the involvement of AGER, ICAM1, NOS2A, PPARG and LTA in DR genesis. However, it is still difficult to draw conclusions for many reported genetic variances due to lack of consistencies between studies.