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Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with
Objective:
To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls.
Methods:
Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients.
Results:
TNFalpha6 showed the strongest association with disease susceptibility. The TNFalpha6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFalpha6 allele had severe disease.
Conclusions:
This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.
Insights
Tumour necrosis factor (TNF) gene polymorphism, specifically the TNFalpha6 allele, is linked to rheumatoid arthritis (RA) susceptibility in Peruvian mestizo patients. HLA-DRB1*1402 also independently increases RA risk in this population.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- Rheumatoid arthritis (RA) is a complex autoimmune disease with a known genetic component.
- Human Leukocyte Antigen (HLA) and Tumour Necrosis Factor (TNF) gene polymorphisms are implicated in RA pathogenesis.
- Genetic associations in diverse ethnic populations require further investigation.
Purpose of the Study:
- To investigate the association between RA and polymorphisms in HLA and TNF genes.
- To compare genetic variations in Peruvian mestizo RA patients with ethnically matched controls.
- To explore the relationship between specific alleles and disease susceptibility and severity.
Main Methods:
- Genotyping of HLA-DRB1, HLA-DQA1, HLA-DQB1, TNFalpha, and TNFbeta alleles using PCR amplification.
- Comparison of allele frequencies between 79 RA patients and 65 healthy controls.
- Assessment of clinical severity in a subset of 35 RA patients.
Main Results:
- The TNFalpha6 allele demonstrated the strongest association with RA susceptibility, being significantly more frequent in patients (p<0.0076).
- The HLA-DRB1*1402 allele, part of the shared epitope, was also significantly increased in patients (p<0.0311).
- The TNFalpha6 allele was more common in patients regardless of the presence of the HLA-DRB1*1402-DQB1*0301-DQA1*0401 haplotype, and its absence correlated with milder disease.
Conclusions:
- TNF gene polymorphism is associated with RA susceptibility in a non-white population for the first time.
- Both TNFalpha6 and HLA-DRB1*1402 alleles independently confer an increased risk for RA in Peruvian mestizo patients.
- These findings highlight the importance of specific genetic factors in RA pathogenesis across different ethnic groups.