Detection of Major Mutations in <i>CFTR</i>, <i>SERPINA1</i>, <i>HFE</i> Genes in Benign Unconjugated Hyperbilirubinemia Phenotype

Detection of Major Mutations in CFTR, SERPINA1, HFE Genes in Benign Unconjugated Hyperbilirubinemia Phenotype

Ivanova А.А., Apartseva N.E., Kashirina A.P., Nemtsova E.G., Ivanova Y.V., Kruchinina M.V., Kurilovich S.A., Maksimov V.N.

Key words: Gilbert’s syndrome; UGT1А1; HFE; CFTR; SERPINA1; nonconjugated hyperbilirubinemia.

2024, volume 16, issue 4, page 38.

DOI: https://doi.org/10.17691/stm2024.16.4.04

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The aim of the study was to search for the associations of benign unconjugated hyperbilirubinemia phenotype with rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) mutations of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) mutations of SERPINA1 gene.

Material and Methods. The study design is case–control. The group with Gilbert’s syndrome (GS) phenotype (n=414; mean age — 36.7±15.9 years; 49.8% men) was formed by gastroenterologists, and included the individuals with unconjugated hyperbilirubinemia who underwent a standard clinical examination. The individuals with known causes of unconjugated hyperbilirubinemia were excluded from the group. The control group (n=429; mean age — 38.5±14.3 years; 52.2% men) was a random sampling from DNA banks of MONICA project participants, the screening of young people aged 25–44 and a one-time study of schoolchildren in Novosibirsk (Russia). DNA was isolated by phenol-chloroform extraction or by the express method (PROBA-RAPID-GENETIKA; DNA-Technology, Moscow, Russia) from venous blood. Genotyping of groups by nucleotide sequence rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene was performed by polymerase chain reaction followed by the analysis of fragment length polymorphism on a polyacrylamide gel.

Results. According to the genotypes and alleles of the variants rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene, no statistically significant differences were found between the GS group and the control group (p>0.05).

Conclusion. Nucleotide sequence variants rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene, or their combinations with rs3064744 of UGT1A1 gene were found to have no association with GS.

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Ivanova А.А., Apartseva N.E., Kashirina A.P., Nemtsova E.G., Ivanova Y.V., Kruchinina M.V., Kurilovich S.A., Maksimov V.N. Detection of Major Mutations in CFTR, SERPINA1, HFE Genes in Benign Unconjugated Hyperbilirubinemia Phenotype. Sovremennye tehnologii v medicine 2024; 16(4): 38, https://doi.org/10.17691/stm2024.16.4.04