title: Cyclic AMP-Responsive Element Modulator α Polymorphisms Are Potential Genetic Risks for Systemic Lupus Erythematosus.
abstract: To investigate whether the cyclic AMP-responsive element modulator α (CREMα) polymorphisms are novel susceptibility factors for systemic lupus erythematosus (SLE), four tag SNPs, rs1057108, rs2295415, rs11592925, and rs1148247, were genotyped in 889 SLE cases and 825 healthy controls. Association analyses were performed on whole dataset or clinical/serologic subsets. Association statistics were calculated by age and sex adjusted logistic regression. The G allele frequencies of rs2295415 and rs1057108 were increased in SLE patients, compared with healthy controls (rs2295415: 21.2% versus 17.8%, OR 1.244, P = 0.019; rs1057108: 30.8% versus 27.7%, OR 1.165, P = 0.049). The haplotype constituted by the two risk alleles "G-G" from rs1057108 and rs2295415 displayed strong association with SLE susceptibility (OR 1.454, P = 0.00056). Following stratification by clinical/serologic features, a suggestive association was observed between rs2295415 and anti-Sm antibodies-positive SLE (OR 1.382, P = 0.044). Interestingly, a potential protective effect of rs2295415 was observed for SLE patients with renal disorder (OR 0.745, P = 0.032). Our data provide first evidence that CREMα SNPs rs2295415 and rs1057108 maybe novel genetic susceptibility factors for SLE. SNP rs2295415 appears to confer higher risk to develop anti-Sm antibodies-positive SLE and may play a protective role against lupus nephritis.
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Su
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C497410:CREM protein, human; D051786:Cyclic AMP Response Element Modulator