title: Gene-gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population.
abstract: The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene-gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case-control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40-2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38-2.13). GMDR analysis suggested a potential gene-gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67-3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.
authors.affiliation: Department of Rheumatism in the Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, 130000, Jilin, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Nie
authors.affiliation: Department of Rheumatism in the Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, 130000, Jilin, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nursing, College of Humanities and Sciences, Northeast Normal University, Changchun, 130000, China.
authors.forename: Guixiu
authors.initials: G
authors.lastname: Yan
authors.affiliation: College of Nursing and Health Science, Nanfang College, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Nursing and Health Science, The University of Texas at Tylar, 3900 University Blvd, Tyler, TX, USA.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Urology and Rheumatism, The Central Hospital of Wuhan, No. 26 Shengli Street, Wuhan, 430014, Hubei, China. zhouwywy667@163.com.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000483:Alleles; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D019013:CD40 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D019013:CD40 Antigens
keywords: CD226; CD40; Interaction; Polymorphism; SLE