Magnusson V, Johanneson B, Lima G, Odeberg J, Alarcón-Segovia D, Alarcón-Riquelme M E
Department of Genetics and Pathology, Section for Medical Genetics, University of Uppsala, Uppsala, Sweden.
Genes Immun. 2004 Mar;5(2):130-7. doi: 10.1038/sj.gene.6364052.
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.
本研究的目的是在系统性红斑狼疮（SLE）患者家庭中分析低亲和力Fcγ受体等位基因的单倍型的连锁情况、结构及传递。采用限制性片段长度多态性（RFLP）、等位基因特异性PCR或焦磷酸测序技术对Fcγ受体多态性FcγRIIA - 131R/H、FcγRIIIA - 176F/V、FcγRIIIB - NA1/2以及FcγRIIB基因中的一个多态性进行基因分型。在多病例家庭中检测个体单核苷酸多态性（SNP）和单倍型的连锁情况，并使用列联表、传递不平衡检验以及瑞典和墨西哥单病例家庭中基于患病家庭的对照组进行关联分析。在多病例家庭中，未检测到Fcγ受体多态性存在连锁或关联。然而，在单病例家庭中发现FcγRIIA - 131R和IIIA - 176F等位基因均与疾病有关联，而IIIB或IIB则未发现关联。对于包含两个风险等位基因的单倍型，发现其与SLE存在等位基因关联，但仅含有其中一个风险等位基因的单倍型则未发现关联。我们提出，FcγRIIA - 131R和FcγRIIIA - 176F均为SLE的风险等位基因，主要通过单一主要单倍型传递，但并非完全如此，该单倍型在功能上类似于复合杂合子的情况。
