OBJECTIVES: Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. METHODS: A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and non-parametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. RESULTS: A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10-8) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. CONCLUSIONS: The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
OBJECTIVES:Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. METHODS: A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and non-parametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. RESULTS: A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10-8) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. CONCLUSIONS: The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
Authors: C J O'Donnell; K Lindpaintner; M G Larson; V S Rao; J M Ordovas; E J Schaefer; R H Myers; D Levy Journal: Circulation Date: 1998-05-12 Impact factor: 29.690
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Authors: O H Kantarci; A Goris; D D Hebrink; S Heggarty; S Cunningham; I Alloza; E J Atkinson; M de Andrade; C T McMurray; C A Graham; S A Hawkins; A Billiau; B Dubois; B G Weinshenker; K Vandenbroeck Journal: Genes Immun Date: 2005-03 Impact factor: 2.676
Authors: E M Tan; A S Cohen; J F Fries; A T Masi; D J McShane; N F Rothfield; J G Schaller; N Talal; R J Winchester Journal: Arthritis Rheum Date: 1982-11
Authors: Amr H Sawalha; Lu Wang; Ajay Nadig; Emily C Somers; W Joseph McCune; Travis Hughes; Joan T Merrill; R Hal Scofield; Faith M Strickland; Bruce Richardson Journal: J Autoimmun Date: 2012-02-03 Impact factor: 7.094
Authors: Chen Yao; Roby Joehanes; Andrew D Johnson; Tianxiao Huan; Tõnu Esko; Saixia Ying; Jane E Freedman; Joanne Murabito; Kathryn L Lunetta; Andres Metspalu; Peter J Munson; Daniel Levy Journal: Hum Mol Genet Date: 2013-11-15 Impact factor: 6.150
Authors: Peter K Gregersen; Roman Kosoy; Annette T Lee; Janine Lamb; Jon Sussman; David McKee; Kim R Simpfendorfer; Ritva Pirskanen-Matell; Frederik Piehl; Qiang Pan-Hammarstrom; Jan J G M Verschuuren; Maarten J Titulaer; Erik H Niks; Alexander Marx; Philipp Ströbel; Björn Tackenberg; Michael Pütz; Angelina Maniaol; Ahmed Elsais; Chantal Tallaksen; Hanne F Harbo; Benedicte A Lie; Soumya Raychaudhuri; Paul I W de Bakker; Arthur Melms; Henri-Jean Garchon; Nicholas Willcox; Lennart Hammarstrom; Michael F Seldin Journal: Ann Neurol Date: 2012-10-10 Impact factor: 10.422