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HLA-A and -DRB4 genes in controlling the susceptibility to Hashimoto's thyroiditis
1Department of Genetics, Medical Institute of Bioregulation, Fukuoka, Japan.
Insights
Human leukocyte antigen (HLA) genes HLA-A2 and DRB4*0101 are linked to heightened susceptibility to hypertension (HT). Conversely, HLA-DQA1*0102 may offer protection against this condition.
Area of Science:
- Immunogenetics
- Human Genetics
- Cardiovascular Disease Research
Background:
- Hypertension (HT) is a complex condition with significant genetic contributions.
- Human Leukocyte Antigen (HLA) genes play a crucial role in immune regulation and have been implicated in various diseases.
Purpose of the Study:
- To investigate the association between specific HLA alleles and the pathogenesis of hypertension.
- To identify HLA-linked genetic factors influencing susceptibility or resistance to HT.
Main Methods:
- Serologic and DNA typing (PCR-SSOP) for HLA-A, -B, -C, -DR, -DQ, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, and -DPB1 genes in 71 HT patients.
- Statistical analysis including relative risk (RR) and odds ratio (OR) calculations to assess associations.
Main Results:
- Significant positive associations found between HT and HLA-A2 (RR=2.03) and HLA-DRB4*0101 (DR53) (RR=4.48).
- The combined presence of HLA-A2 and DRB4*0101 significantly increased the odds of HT risk (OR=12.8).
- A decreased frequency of HLA-DQA1*0102 in patients suggests a potential protective role against HT.
Conclusions:
- At least two loci, HLA-A and HLA-DRB4, appear to jointly influence susceptibility to hypertension.
- The HLA-DQA1*0102 allele may confer resistance to the development of HT.
Abstract:
HLA-linked genetic factors involved in the pathogenesis of HT were studied in 71 patients with HT by serologic typing for HLA-A, -B, -C, -DR, and -DQ specificities and by DNA typing for HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, AND -DPB1 genes using the PCR-SSOP method. Typing results demonstrated significant positive associations of HT with HLA-A2 and -DRB4*0101 (DR53) (p < 0.01, RR = 2.03, EF = 0.61 and p < 0.0001, RR = 4.48, EF = 0.69, respectively). Although HLA-DR8, -DRB1*0403, -DQA*03, and -DQB1*0303 were statistically more prevalent in the patient group than in the controls, these associations were presumably due to the strong linkage disequilibria of these alleles with HLA-A2 or -DRB4*0101 in the Japanese population. Ninety-seven percent of the patients (69 out of 71) were positive for HLA-A2 or -DRB4*0101 compared to 79% in controls (RR = 8.7, p < 0.0005). The combination of HLA-A2 and -DRB4*0101 showed higher OR of risk for HT (OR = 12.8) than HLA-A2 (OR = 7.3) or DRB4*0101 (OR = 7.5) alone. These observations suggest that at least two loci, HLA-A and HLA-DRB4 together, may control the susceptibility to HT. On the other hand, the frequency of DQA1*0102 was significantly decreased in the patient group, suggesting that DQA1*0102 might confer resistance to HT.