Correlation Between HLA-DRB1, HLA-DQB1 Polymorphism and Autoantibodies Against Angiotensin AT1 Receptors in Chinese Patients With Essential Hypertension

Background: The autoantibodies (AAs) against angiotensin AT(1) receptors (AT(1)-AAs) have been discovered in patients with preeclampsia, malignant hypertension, and essential hypertension (EH); however, the mechanism of AA production remains to be investigated. Hypothesis: Polymorphisms of HLA-DRB1 or HLA-DQB1 are related to production of AAs in autoimmune diseases. We hypothesis that the polymorphisms of the HLA molecules are also associated with production of AT(1)-AAs in patients with EH. Methods: We enrolled 394 patients with EH and 224 normotensive subjects in this study. Autoantibodies in sera of donors were detected by enzyme-linked immunosorbent assay. The subjects' clinical data were collected, including gender, age, body mass index, blood pressure, smoking status, and diabetes. The patients and the normotensive subjects were classified respectively into AA-positive and AA-negative groups. Typing of DNA for HLA-DRB1 and HLA-DQB1 alleles was done by polymerase chain reaction amplification with sequence-specific primers. Results: Thirteen HLA-DRB1 and 7 HLA-DQB1 alleles were found in this population. The frequencies of AT(1)-AAs were related to blood pressure level. The frequency of AT1-AAs in the EH group was higher than that in the normotensive group (P = 0.0001). The levels of AAs in different groups of EH show a significant difference (P = 0.027). In addition, HLA-DRB1*04 and HLA-DRB1*14 (odds ratio [OR]: 3.06, 95% confidence interval [CI]: 1.56-5.97, P = 0.001; and OR: 2.53, 95% CI: 1.080-5.91, P = 0.033, respectively) were related to AT(1)-AA production in normotensive subjects after adjusting for covariants. The HLA-DRB1*04 allele might be related to AT(1)-AA production in hypertensive subjects, and the P value was of baseline statistical significance after adjusting for blood pressure and other covariants (OR: 1.63, 95% CI: 0.95-2.78, P = 0.070). Conclusions: These results suggest a difference in the immunogenetic background between the positive and negative AAs with hypertension or normotension. The HLA-DRB1*04 allele increases the risk for AT(1)-AA production.