Aim: To investigate potential association between HLA variation and Sudden Cardiac Death (SCD) and other acute, potentially lethal cardiac conditions. In addition to traditional factors contributing to risk of SCD such as inherited heart muscle diseases, trauma and/or arrhythmic syndromes, inflammation was implicated as an independent risk factor. An important role in inflammatory response was attributed to immune system genes, the most polymorphic of which are HLA genes.
Method: 101 patients with acute cardiac conditions, 6 HLA loci (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPB1) were genotyped by NGS . Observed allele/phenotype frequencies were then compared with those determined in a control population of 141 healthy individuals; all investigated subjects were unrelated and of the Czech ethnicity.
Results: The comparisons revealed an overrepresentation of HLA-DPB1*23:01 in the patient group in comparison with control population (Odds Ratio, OR 5.6, p=0.02). The subanalysis showed this increase to be most prominent in 30 patients with SCD (OR 9.8, p=0.01) and/or 16 patients with ventricular fibrillation (OR 14.1, p=0.01). Apart from findings of this HLA-class II risk variant, HLA-B *35:01 was more frequent in SCD patients (OR 4.1, p=0.01). Regarding other disease subgroups, HLA-DQB1*04:02 was inversely associated (i.e. protective: OR 0.5, p=0.01) with aortic rupture while HLA-DRB1*04:02 conferred risk to this condition (OR 13.7, p=0.03). HLA-B*49:01 associated with vetricular tachycardia (OR 6.5, p=0.03). Reported values are based on allele frequency data, similar observations resulted when phenotype frequencies (carriage rates) were analyzed. No association, however, persisted after strict correction for multiple comparisons.
Conclusion: By reporting data from our ongoing study of a plausible relationship between HLA variation and severe acute cardiac conditions, namely SCD, we wish to disseminate the information and search for collaborators to embark on a multicentre project with expanded patients numbers and populations. In parallel, implication of HLA-DPB1*23:01 in the most critical conditions such as SCD and/or cardiac fibrillation, as well as other suggested associations, must be considered preliminary unless replicated in other centres/populations. Supported: Min. Health Czech Rep. – RVO (FNOL, 00098892), IGA PU_LF_2024_005
