RESUMO
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.
Assuntos
Alelos , Antígenos CD/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Receptores de IgG/genética , Ligação Genética/genética , Genótipo , Haplótipos/genética , Humanos , México , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , SuéciaRESUMO
We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.
Assuntos
Genes bcl-2 , Lúpus Eritematoso Sistêmico/genética , Alelos , Sequência de Bases , Estudos de Casos e Controles , Estudos de Coortes , Primers do DNA/genética , Feminino , Frequência do Gene , Ligação Genética , Genótipo , Humanos , Interleucina-10/genética , Lúpus Eritematoso Sistêmico/imunologia , Masculino , México , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , SuéciaRESUMO
OBJECTIVE: To study the contribution of the IL10 gene to the susceptibility to systemic lupus erythematosus (SLE). METHODS: Analysis by fluorescent-semiautomated genotyping of a dinucleotide repeat located in the promoter region of the IL10 locus (microsatellite G). RESULTS: No significant difference was found in the frequencies of the microsatellite alleles of 330 Mexican patients with SLE compared to 368 controls from the same population. Two-point linkage analyses were carried out using 13 Mexican, 13 Swedish, and 8 Icelandic families with 2 or more cases with SLE. No linkage was revealed between IL10 and SLE, using a variety of parameter settings. CONCLUSION: Our results do not support that the IL10 gene contributes to the susceptibility to SLE in the populations we studied.
Assuntos
Interleucina-10/genética , Lúpus Eritematoso Sistêmico/genética , Repetições de Dinucleotídeos/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , México , Repetições de Microssatélites , Regiões Promotoras Genéticas/genéticaRESUMO
Systemic lupus erythematosus is a disease of unknown etiology. Multiple genetic factors are believed to be involved in its pathogenesis. In addition, and due to genetic heterogeneity, these factors and/or their combinations may be different in different ethnic groups, while some might be shared between populations. We have performed genome scans in multicase families from three different population groups, two from Northern Europe, with a high degree of homogeneity, and the third from a recently admixed population of Mexican Mestizos. Although our family material is relatively small, the results presented here show that using family sets from well defined populations are sufficient to detect susceptibility loci for SLE. Our results also reveal the chromosomal regions most likely to contain susceptibility genes for SLE.