title: Association of interleukin-10 promoter haplotypes with disease susceptibility and IL-10 levels in Mexican patients with systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is the prototype autoimmune rheumatic disease. The etiology of this disease is incompletely understood; however, environmental factors and genetic predisposition are involved. Cytokine-mediated immunity plays a crucial role in the pathogenesis of SLE. We investigate the association of interleukin-10 (IL-10) promoter polymorphisms and their haplotypes in SLE patients from the western Mexico. One hundred and twenty-five SLE patients fulfilling the 1997 ACR criteria and 260 unrelated healthy subjects (HS), both Mexican mestizos, were genotyped for IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms. Haplotypes were inferred using the expectation-maximization algorithm, then allele and haplotype distributions were compared between patients and HS, as well as patients with different clinical variables. We identified at -1082, -819, and -592 four predominant haplotypes ACC (43.70 % in patients vs 46.55 % in HS), ATA (21.45 vs 22.97 %), GCC (16.28 vs 14.21 %), and GTA (14.12 vs 14.12 %). The ATC haplotype was more frequent in SLE respect to HS, suggesting a risk effect (3.23 vs 1.05 %; OR 3.55, CI 1.14-11.11; p = 0.0293). SLE patient carriers of -592 CC genotype as well as the dominant model of inheritance showed higher sIL-10 respect to AA genotype, suggesting that -592 C allele is associated with increased production of the cytokine (p < 0.05). The ACC haplotype had higher IL-10 serum levels and higher values of Mexican version of the Systemic Lupus Erythematosus Disease Activity Index compared with the other haplotype carriers; however, no association was found regarding autoantibodies. Our data suggest that the IL-10 promoter haplotypes play an important role in the risk of developing SLE and influence the production of IL-10 in Mexican population. Nevertheless, further studies are required to analyze the expression of mRNA as well as to investigate the interacting epigenetic factors that could help to define the true contribution of this marker in SLE pathogenesis.
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.|Departamento de Inmunología y Reumatología del Hospital General de Occidente, Secretaria de Salud Jalisco, Zapopan, Jalisco, México.
authors.forename: Claudia Azucena
authors.initials: CA
authors.lastname: Palafox-Sánchez
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Edith
authors.initials: E
authors.lastname: Oregon-Romero
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Diana Celeste
authors.initials: DC
authors.lastname: Salazar-Camarena
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Yeminia Maribel
authors.initials: YM
authors.lastname: Valle
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Jesús René
authors.initials: JR
authors.lastname: Machado-Contreras
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Mariana
authors.initials: M
authors.lastname: Orozco-López
authors.affiliation: Departamento de Inmunología y Reumatología del Hospital General de Occidente, Secretaria de Salud Jalisco, Zapopan, Jalisco, México.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Orozco-Barocio
authors.affiliation: Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vázquez-Del Mercado
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México. biologiamolecular@hotmail.com.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10
keywords: Genetic risk factors; IL-10 haplotypes; IL-10 polymorphisms; Systemic lupus erythematosus