title: Genetic association of complement component 2 polymorphism with systemic lupus erythematosus.
abstract: Complement component 2 (C2), an early member of the classical pathway, mainly participates in apoptotic cell clearance. We hypothesize that C2 polymorphism may confer genetic susceptibility to complement dysfunction in systemic lupus erythematosus (SLE). The major aim of our study was to investigate the clinical and serological associations of C2 variants in Chinese patients with SLE. The single-nucleotide polymorphism (rs2844455, G/A SNP) located in the intron region of C2 gene was genotyped by direct sequencing in 95 SLE patients and 95 matched normal control subjects. The gene expression profiles were generated by quantitative real-time polymerase chain reaction (PCR) and reverse transcription PCR. Our results showed that the AA genotype was observed more frequently in SLE patients than in normal control subjects (22.1% vs 9.5%, P < 0.05). The A allele was strongly associated with the occurrence of hair loss, photosensitivity and anti-cardiolipin antibodies; whereas, the G allele was associated with lower frequencies of these clinical presentations. Relative expression levels were significantly lower in patients with the AA genotype [median: 18.86, interquartile range (IQR) 11.36-22.43, P = 0.002] than in those with the GG genotype (35.76, IQR: 19.33-49.71). As expected, we confirmed the A allele as a risk factor for SLE development in a Chinese population, in contrast, the G allele might be a protective factor against the pathogenic autoantibody formation and cutaneous manifestations in SLE patients.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: H-H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: K-R
authors.initials: KR
authors.lastname: Lee
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: W-T
authors.initials: WT
authors.lastname: Hung
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: D-Y
authors.initials: DY
authors.lastname: Chen
mesh_terms: D000328:Adult; D000483:Alleles; D000505:Alopecia / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017153:Antibodies, Anticardiolipin / Q000097:blood; D044466:Asian People; D016022:Case-Control Studies; D003175:Complement C2 / Q000235:genetics* / Q000276:immunology; D005091:Exons; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020795:Photophobia / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D017153:Antibodies, Anticardiolipin; D003175:Complement C2
keywords: anti-cardiolipin antibody; complement component 2; photosensitivity; single-nucleotide polymorphism; systemic lupus erythematosus