title: Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and susceptibility to autoimmune diseases.
abstract: Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.
authors.affiliation: Servicio de Inmunología, Instituto de Biomedicina, Hospital Universitario Virgen del Rocío, Avda Manuel Siurot s/n, 41013, Seville, Spain.
authors.forename: José Raúl
authors.initials: JR
authors.lastname: García-Lozano
authors.forename: Cristina
authors.initials: C
authors.lastname: Abad
authors.forename: Ana
authors.initials: A
authors.lastname: Escalera
authors.forename: Belén
authors.initials: B
authors.lastname: Torres
authors.forename: Olga
authors.initials: O
authors.lastname: Fernández
authors.forename: Alicia
authors.initials: A
authors.lastname: García
authors.forename: Julio
authors.initials: J
authors.lastname: Sánchez-Román
authors.forename: José-Mario
authors.initials: JM
authors.lastname: Sabio
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Enrique
authors.initials: E
authors.lastname: Raya-Alvarez
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: María Francisca
authors.initials: MF
authors.lastname: González-Escribano
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology; D001669:Biochemical Phenomena; D004198:Disease Susceptibility / Q000150:complications / Q000276:immunology; D005091:Exons; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007159:Immunologic Tests; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics / Q000276:immunology; D010829:Physiological Phenomena; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger