title: Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population.
abstract: Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07±1.60) than healthy controls (7.02±1.64) (P=1.63 × 10(-12)). Significant gene-gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11-13 risk alleles were 4.17 (95% confidence interval (CI) 1.89-9.19, P=0.0002) and 8.77 (95% CI 1.92-40.0, P=0.0016), respectively. In contrast, subjects with ≤4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03-0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying ≥10 risk alleles than those with <10 (OR 2.30, CI 1.09-4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation.
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.forename: Aya
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Ikue
authors.initials: I
authors.lastname: Ito
authors.forename: Takumi
authors.initials: T
authors.lastname: Furuya
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Chieko
authors.initials: C
authors.lastname: Kyogoku
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Taichi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Makio
authors.initials: M
authors.lastname: Kusaoi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
mesh_terms: D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D016017:Odds Ratio; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics
chemical_list: D059811:HLA-DRB1 Chains; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D050797:STAT4 Transcription Factor