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 Fcγ receptors. The Fcγ receptor polymorphisms FcγRIIA-131R/H, FcγRIIIA-176F/V and FcγRIIIB-NA1/2 and a polymorphism in the FcγRIIB 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 FcγR polymorphisms in the multicase families. However, an association was found for both FcγRIIA-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 FcγRIIA-131R and FcγRIIIA-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.
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Acknowledgements
We acknowledge the technical support given by Kicki Holmberg from KTH Genome Center. The Wallenberg Consortium North supported genotyping at the KTH Genome Center. All microsatellite genotyping was performed at the Uppsala Genotyping Center supported by the Swedish Foundation for Strategic Research. This work was supported by grants from the Swedish Science Council (12673), the Gustaf V: 80th-year Jubilee Foundation, the Swedish Association against Rheumatism and the Börje Dahlins Foundation.
The members of Collaborative Group on the Genetics of SLE who have provided samples for the multiplex families are: Antonio Iglesias, Eduardo Egea and Gloria Egea (Colombia); Ignacio García de la Torre (Mexico); Ralph Williams Jr (USA); Kok-Yok Fong (Singapore); Mauro Galeazzi, Sergio Milgiarese, Domenico Sebastiani and Ornella de Pitá (Italy); K Boki, Maria Kastorida and Haralampos Moutsopoulos (Greece); Helga Kristjansdottir, Kristján Steinsson and Gerdur Gröndal (Iceland); Roland Jonsson and Anne-Isine Bolstad (Norway); Elisabet Svennungsson, Iva Gunnarsson, Gunnar Sturfelt and Lennart Truedsson (Sweden) and Caroline Gordon (UK).
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Magnusson, V., Johanneson, B., Lima, G. et al. Both risk alleles for FcγRIIA and FcγRIIIA are susceptibility factors for SLE: a unifying hypothesis. Genes Immun 5, 130–137 (2004). https://doi.org/10.1038/sj.gene.6364052
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DOI: https://doi.org/10.1038/sj.gene.6364052
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