title: Genetic association of IRF5 with SLE in Mexicans: higher frequency of the risk haplotype and its homozygozity than Europeans.
abstract: The IRF5 gene was found to be strongly associated with SLE. We identified two functional polymorphisms and recently an insertion/deletion together with a tag SNP defining the risk haplotype in individuals of European ancestry. We now analyzed sets of Mexican patients with SLE. Three polymorphisms in the IRF5 gene were genotyped in two sets of Mexican individuals with SLE and controls as well as in families including a set of pediatric SLE patients. A set of healthy Mexican Indians was also typed. Genetic association with SLE was found for all three polymorphisms. The genetic association was very strong in the case-control analysis in both sets (for SNP rs2070197, combined P = 1.26 x 10(-21)) and in families (combined P = 0.000004). Compared to healthy individuals with European ancestry, the frequency of the risk haplotype in healthy Mexican individuals was significantly higher and even higher in the healthy Mexican Indian group. Further, a much higher frequency of the risk haplotype and of individual homozygote for it was found among Mexican SLE patients. The significantly higher frequency of homozygote individuals for the risk haplotype among Mexican SLE patients could be the result of genetic admixture, and suggests the possibility that IRF5 could be involved in the more active disease and organ involvement known to occur among Mexican SLE patients.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Dag Hammarsjkölds väg 20, 751 85 Uppsala, Sweden.
authors.forename: M V Prasad Linga
authors.initials: MV
authors.lastname: Reddy
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Vicente
authors.initials: V
authors.lastname: Baca
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005006:Ethnicity / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008800:Mexico; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors