RESUMO
OBJECTIVE: To analyse the influence of shared epitope positive HLA-DRB1 alleles (QKRAA or QRRAA)) on rheumatoid arthritis (RA) susceptibility and severity in Chileans, a population that exhibits a weak association with HLA-DR4. METHODS: Prevalence of alleles DRB1*01 and DRB1*04 alleles was determined by polymerase chain reaction amplification and sequence specific oligonucleotide hybridisation in 129 RA patients with defined clinical features and in 97 healthy controls. RESULTS: The shared epitope was found in 70 (54%) of the RA patients and in 29 (30%) of controls (odds ratio (OR) = 3; 95% confidence intervals (CI) = 1.5, 5.1; p = 0.0004), and was present in a double dose in 20% of patients versus 4% of controls (OR = 6; 95% CI = 2, 21; p = 0.0009). HLA-DRB1*0403 was the most prevalent DR4 subtype in controls (19%). HLA-DRB1*0403 or *0408 were the alleles most prominently associated with RA, 19% versus 6% in controls (OR = 3; 95% CI = 1.3, 10; p = 0.01). The risk of RA in those carrying a double dose of the shared epitope was 7.5 times that seen in patients lacking the epitope. Disease severity was moderate: 33% had extra-articular manifestations. The double dose was associated with an increased risk of vasculitis or extra-articular manifestations. However, 59 patients (46%) did not carry the shared epitope and 18 of them (31%) had extra-articular manifestations. CONCLUSIONS: The weak association of RA with DR4 in Chileans seems to relate to a relatively high frequency of the DRB1*0403 allele among DR4 subtypes. As in other populations, the shared epitope in double dose is associated with RA development, especially in its more severe forms. However, both development and expression of severe forms of the disease were independent of the shared epitope in a high proportion of patients, thus emphasising the genetic heterogeneity of the disease and the possible involvement of other genetic elements.
Assuntos
Alelos , Artrite Reumatoide/imunologia , Antígenos HLA-DR/genética , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Chile/epidemiologia , Suscetibilidade a Doenças , Feminino , Antígeno HLA-DR4 , Cadeias HLA-DRB1 , Homozigoto , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Prevalência , Fatores de RiscoRESUMO
The polymorphism of complement component C3, BF and C4 was studied in an urban population of Bogota, Colombia and for C3 and BF, genetic heterogeneity was further examined among the five villages of the Colombian Andes. For both C3 and BF systems there is considerable variation of allele frequencies among the five villages and overall there is significant heterogeneity among the six population groups studied.
Assuntos
Complemento C3/genética , Complemento C4/genética , Fator B do Complemento/genética , Precursores Enzimáticos/genética , Polimorfismo Genético , Alelos , Colômbia , Frequência do Gene , Variação Genética , Humanos , Fenótipo , População Rural , População UrbanaRESUMO
Genetic polymorphism of red cell enzymes glutamate-pyruvate transaminase (GPT) and glyoxalase I (GLO) was investigated in five villages of the Colombian Andes. The GPT1 and GLO1 gene frequencies show a considerable range, but compatible to the range of European populations. In both the systems there is slight excess of observed homozygosity suggesting that the infrastructure of the subpopulations may be influenced by inbreeding.