title: Genetic Investigation of Complement Pathway Genes in Type 2 Diabetic Retinopathy: An Inflammatory Perspective.
abstract: Diabetic retinopathy (DR) has complex multifactorial pathogenesis. This study aimed to investigate the association of complement pathway genes with susceptibility to DR. Eight haplotype-tagging SNPs of SERPING1 and C5 were genotyped in 570 subjects with type 2 diabetes: 295 DR patients (138 nonproliferative DR [NPDR] and 157 proliferative DR [PDR]) and 275 diabetic controls. Among the six C5 SNPs, a marginal association was first detected between rs17611 and total DR patients (P = 0.009, OR = 0.53 for recessive model). In stratification analysis, a significant decrease in the frequencies of G allele and GG homozygosity for rs17611 was observed in PDR patients compared with diabetic controls (Pcorr = 0.032, OR = 0.65 and Pcorr = 0.016, OR = 0.37, resp.); it was linked with a disease progression. A haplotype AA defined by the major alleles of rs17611 and rs1548782 was significantly predisposed to PDR with increased risk of 1.54 (Pcorr = 0.023). Regarding other variants in C5 and SERPING1, none of the tagging SNPs had a significant association with DR and its subgroups (all P > 0.05). Our study revealed an association between DR and C5 polymorphisms with clinical significance, whereas SERPING1 is not a major genetic component of DR. Our data suggest a link of complement pathway with DR pathogenesis.
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; The Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150001, China.
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Operating Room, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yun Duan
authors.initials: YD
authors.lastname: Sun
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jiao Jie
authors.initials: JJ
authors.lastname: Fan
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yan Bo
authors.initials: YB
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003174:Complement C1 Inactivator Proteins / Q000235:genetics; D050718:Complement C1 Inhibitor Protein; D003182:Complement C5 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003182:Complement C5; C469952:SERPING1 protein, human