Genetic polymorphisms related to the vitamin D pathway in patients with cirrhosis with or without hepatocellular carcinoma (HCC)

4 May 2022
Beatriz de Jesus Brait, Simone Perpétua da Silva Lima, Franciana Luísa Aguiar, Rafael Fernandes-Ferreira, Camila Ive Ferreira Oliveira-Brancati, Joyce Aparecida Martins Lopes Ferraz, Graciela Domitila Tenani, Marcela Augusta de Souza Pinhel, Leticia Carolina Paraboli Assoni, Augusto Haniu Nakahara, Natalia dos Santos Jábali, Octavio Pennella Fenelon Costa, Maria Eduarda Lopes Baitello, Sidney Pinheiro Júnior, Renato Ferreira Silva, Rita de Cássia Martins Alves Silva, Doroteia Rossi da Silva Souza

Objective: To evaluate the association of genetic polymorphisms of vitamin D transporter protein (DBPrs4588 and DBP-rs7041) and cytochrome P450-24A1 (CYP24A1-rs6013897) in patients with cirrhosis with or without hepatocellular carcinoma (HCC), including demographic/clinical/biochemical profiles.

Methods: A total of 383 individuals were studied, considering the total group (TotalG) of patients with cirrhosis (TotalG: N = 158) with or without HCC, distributed into Group 1 (G1): cirrhosis and HCC; Group 2 (G2): isolated cirrhosis; and 225 individuals without hepatopathies (G3). Polymorphisms were analysed by real-time polymerase chain reaction. An alpha error of 5% was admitted.

Results: CYP24A1-rs6013897 predominated the genotype with at least one polymorphic allele (_/T) in G1 (98.3%) versus G2 (88.8%; p = 0.0309). There was a moderate positive correlation between vitamin D and parathyroid hormone in patients (TotalG: R2 = 0.3273). Smoking, alcoholism and diabetes mellitus (DM) stood out as independent factors for cirrhosis, as well as for cirrhosis with HCC, except for smoking, adding, in this case, advanced age, male gender, polymorphic allele of CYP24A1-rs6013897, viral hepatitis and high levels of serum gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and creatinine. An increase in survival was observed in the presence of the polymorphic allele of DBP-rs7041 (p = 0.0282).

Conclusion: CYP24A1-rs6013897 is associated with cirrhosis and HCC as a predictor, while DBP-rs4588 is associated with reduced vitamin D, and DBP-rs7041 provides increased survival, suggesting a protective characteristic. Advanced age, alcoholism, DM, viral hepatitis and high levels of GGT, AFP and creatinine are also confirmed as predictors of HCC and cirrhosis, while smoking, alcoholism and DM for isolated cirrhosis only.

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