Combination of HLA-DRB1 alleles as a factor causing risks of sporadic congenital heart defects and congenital malformations without chromosome diseases

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A.V. Shabaldin1,2, A.V. Tsepokina1, O.V. Dolgikh3, E.V. Shabaldina2, A.V. Ponasenko1


1Scientific Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovyi Blvd., Kemerovo, 650002, Russian Federation
2Kemerovo State Medical University, 22a Voroshilova Str., Kemerovo, 650056, Russian Federation
3Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation


Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes.
Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies.
We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research.
Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children.
Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

major histocompatibility complex, HLA-DRB1, alleles, congenital heart diseases, congenital malformations, risk factor, married couples, spouse compatibility
Shabaldin A.V., Tsepokina A.V., Dolgikh O.V., Shabaldina E.V., Ponasenko A.V. Combination of hla-drb1 alleles as a factor causing risks of sporadic congenital heart defects and congenital malformations without chromosome diseases. Health Risk Analysis, 2021, no. 1, pp. 133–142. DOI: 10.21668/health.risk/2021.1.14.eng
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