title: Both risk alleles for FcgammaRIIA and FcgammaRIIIA are susceptibility factors for SLE: a unifying hypothesis.
abstract: The aim of this study was to analyze in families with SLE for the presence of linkage and the structure and transmission of haplotypes containing alleles for the low-affinity Fcgamma receptors. The Fcgamma receptor polymorphisms FcgammaRIIA-131R/H, FcgammaRIIIA-176F/V and FcgammaRIIIB-NA1/2 and a polymorphism in the FcgammaRIIB gene were genotyped with RFLP, allele-specific PCR or pyrosequencing. Individual SNPs and haplotypes were tested for linkage in multicase families and for association using contingency tables, transmission disequilibrium test and affected family-based control groups in Swedish and Mexican single-case families. No linkage or association could be detected using the FcgammaR polymorphisms in the multicase families. However, an association was found for both FcgammaRIIA-131R and IIIA-176F alleles in the single-case families, but not for IIIB or IIB. Allelic association to SLE was found for a haplotype that included both risk alleles, but not in haplotypes where only one or the other was present. We propose that FcgammaRIIA-131R and FcgammaRIIIA-176F are both risk alleles for SLE transmitted primarily, but not exclusively on a single major haplotype that behaves functionally in a situation similar to that of compound heterozygozity.
authors.affiliation: Department of Genetics and Pathology, Section for Medical Genetics, University of Uppsala, Uppsala, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Magnusson
authors.forename: B
authors.initials: B
authors.lastname: Johanneson
authors.forename: G
authors.initials: G
authors.lastname: Lima
authors.forename: J
authors.initials: J
authors.lastname: Odeberg
authors.forename: D
authors.initials: D
authors.lastname: Alarcón-Segovia
authors.forename: M E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008800:Mexico; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D013548:Sweden
chemical_list: D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG