The genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy in Chongqing Han population_Chinese Journal of Ocular Fundus Diseases

Authors：

XuDengfeng , YiHong , QiaoYanbin ,  DengWeiwei

Department of Ophthalmology, Chongqing People′s Hospital, Chongqing 400014, China (Xu Dengfeng, Yi Hong, Qiao Yanbin); Department of Comprehensive Medical Oncology, Chongqing Three Gorges Central Hospital, Chongqing 404000, China (Deng Weiwei);

Corresponding author：

DengWeiwei, Email: lsxqweiwei@163.com

Keywords：

Diabetic retinopathy/etiology; Diabetic retinopathy/genetics; Complement C5/genetics; Genes/genetics; Polymorphism,single nucleotide/genetics

DOI：

10.3760/cma.j.issn.1005-1015.2016.02.004

Video：

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Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population. Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age- and sex-matched healthy controls (control group) were enrolled in this study. There were 8 PDR patients in case group. All the subjects were Han ethnic people. The immune-related representative SNP locus of C5 gene including rs2269067, rs7040033, rs7027797 were screened by linkage disequilibrium analysis. Locus rs1017119 was selected by TagSNP and was around the above three loci. Subjects′ peripheral venous blood was collected and DNA was extracted. Genotyping was examined by PCR-restriction fragment length polymorphism method. The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay. Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4×10^-5, OR=1.87, 95%CI=1.43 - 2.44；P=3.1×10^-6). There was no differences in frequency of G, CC and CG genotype of rs2269067 between two groups (P=1.4×10^-4, 1.000, 1.0×10^-6). There were no differences in frequency of G, CC, CG, GG genotype of rs7040033, rs1017119, and rs7027797 between two groups (P > 0.05). The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004). An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003, 0.001). Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.

Citation： XuDengfeng, YiHong, QiaoYanbin, DengWeiwei. The genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy in Chongqing Han population. Chinese Journal of Ocular Fundus Diseases, 2016, 32(2): 126-129. doi: 10.3760/cma.j.issn.1005-1015.2016.02.004 Copy

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1. Xu H,Cai M, Zhang X. Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats [J]. Graefe′s Arch Clin Exp Ophthalmol,2015,253(9):1485-1492.DOI:10.1007/s00417-014-2842-9.
2. Yoshida S, Kubo Y, Kobayashi Y, et al. Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema [J]. Br J Ophthalmol,2015, 99(7):960-966.DOI:10.1136/bjophthalmol-2014-306366.
3. Mehta G, Scheinman RI, Holers VM, et al. A new approach for the treatment of arthritis in mice with a novel conjugate of an anti-C5aR1 antibody and C5 small interfering RNA [J]. J Immunol,2015,194(11):5446-5454.DOI: 10.4049/jimmunol. 1403012.
4. Xu D, Hou S, Jiang Y, et al. Complement C5 Gene Confers Risk for Acute Anterior Uveitis[J]. Invest Ophthalmol Vis Sci [J]. 2015,56(8):4954-4960. DOI: 10.1167/iovs.15-16645.
5. Prechl J, Papp K, Hérincs Z, et al. Serological and genetic evidence for altered complement system functionality in systemic lupus erythematosus: findings of the GAPAID consortium [J/OL]. PLoS One,2016,11(3):0150685 [2016-03-07]. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150685.DOI:10.1371/journal.pone.0150685.
6. Muramatsu D, Wakabayashi Y, Usui Y. Correlation of complement fragment C5a with inflammatory cytokines in the vitreous of patients with proliferative diabetic retinopathy [J]. Graefe′s Arch Clin Exp Ophthalmol,2013, 251(1):15-17.DOI: 10.1007/s00417-012-2024-6.
7. Welikala RA, Fraz MM, Dehmeshki J, et al. Genetic algorithm based feature selection combined with dual classification for the automated detection of proliferative diabetic retinopathy [J]. Comput Med Imaging Graph,2015, 43:64-77.DOI: 10.1016/j.compmedimag.2015.03.003.
8. Sesti LF, Crispim D, Canani LH, et al. The -308G > a polymorphism of the TNF gene is associated with proliferative diabetic retinopathy in Caucasian Brazilians with type 2 diabetes [J]. Invest Ophthalmol Vis Sci,2015, 56(2):1184-1190.DOI: 10.1167/iovs.14-15758.
9. Park YG, Roh YJ. New diagnostic and therapeutic approaches for preventing the progression of diabetic retinopathy [J/OL]. J Diabetes Res,2016,2016: 1753584 [2015-11-02]. http://dx.doi.org/10.1155/2016/1753584. DOI:10.1155/2016/1753584.
10. Chang M, Rowland CM, Garcia VE, et al. A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33.2 [J/OL]. PLoS Genet, 2008, 4(6):1000107[2008-06-27]. http://www.naracstudy.org/NaracStudy/documents/Chang%20PlosGen%202008.pdf. DOI: 10.1371/journal.pgen.1000107.
11. Seddon JM, Yu Y, Miller EC, et al. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration [J]. Nat Genet, 2013, 45(11):1366-1370.DOI:10.1038/ng.2741.
12. Baas DC, Ho L, Ennis S, et al. The complement component 5 gene and age-related macular degeneration [J]. Ophthalmology, 2010,117(3):500-511.DOI:10.1016/j. ophtha.2009.08.032.
13. Zhang X, Li W, Jiang L,et al. Association between polymorphism in TRAF1/C5 gene and risk of rheumatoid arthritis:a meta-analysis [J]. Mol Biol Rep, 2014, 41(1): 317-324.
14. Zhernakova A, Stahl EA, Trynka G,et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci [J/OL]. PLoS Genet, 2011, 7(2):1002004[2011-02-24].http://dx.plos.org/10.1371/jaurnal.pgen.1002004.. DOI:10.1371/journal.pgen.1002004.
15. Kurreeman FA, Goulielmos GN, Alizadeh BZ, et al. The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases [J]. Ann Rheum Dis,2010,69(4):696-699.DOI:10.1136/ard.2008.106567.
16. Hong SB, Lee JJ, Kim SH, et al. The effects of adiponectin and inflammatory cytokines on diabetic vascular complications in obese and non-obese patients with type 2 diabetes mellitus [J]. Diabetes Res Clin Pract,2016,111:58-65.DOI: 10.1016/j.diabres.2015.10.017.
17. Takeuchi M, Sato T, Tanaka A, et al. Elevated levels of cytokines associated with th2 and th17 cells in vitreous fluid of proliferative diabetic retinopathy patients [J/OL]. PLoS One, 2015, 10(9):0137358[2015-09-09]. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137358. DOI:10.1371/journal.pone.0137358.
18. Copland DA, Hussain K, Baalasubramanian S, et al. Systemic and local anti-C5 therapy reduces the disease severity in experimental autoimmune uveoretinitis [J]. Clin Exp Immunol,2010, 159(3):303-314. DOI:10.1111/j.1365-2249.2009.04070.x.

Chinese Journal of Ocular Fundus Diseases

The genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy in Chongqing Han population

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