Genetic Polymorphisms in Bulgarian Children with Non-alcoholic Fatty Liver Disease

Authors

  • Denitza Kofinova Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia
  • Iglika Yordanova Genetic Medico-Diagnostic Laboratory Genica and Department of Medical Chemistry and Biochemistry, Medical University of Sofia
  • Petyo Hadzhiyski Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia
  • Rayna Shentova-Eneva Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia
  • Mila Baycheva Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia
  • Albena Todorova Genetic Medico-Diagnostic Laboratory Genica and Department of Medical Chemistry and Biochemistry, Medical University of Sofia
  • Daniela Avdjieva-Tzavella Department of Clinical Genetics, University Pediatric Hospital “Prof. Dr. Ivan Mitev” and Department of Pediatrics, Medical University of Sofia, Bulgaria

DOI:

https://doi.org/10.7546/CRABS.2022.06.16

Keywords:

children, GCKR P446L, NAFLD, PNPLA3 I148M, TM6SF2 E167K

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, highly prevalent liver disease in children. There is growing evidence that some genetic variants are associated with its development and rapid progression. The aim of this study was to assess the prevalence of specific single-nucleotide polymorphisms – PNPLA3 I148M, GCKR P446L, TM6SF2 E167K in Bulgarian children with NAFLD.

We conducted a single-centre, prospective study of 32 children (22 patients with NAFLD and 10 healthy controls). Genetic testing and abdominal ultrasound were performed in all study participants. In the patients with NAFLD were additionally analyzed anthropometric parameters and standard biochemical tests, 10 of them underwent a liver biopsy for assessing disease activity and fibrosis.

The most common polymorphism was GCKR P446L, detected in 75% of the studied population, followed by PNPLA3 I148M (50.0% of the studied population) and TM6SF2 E167K (9.4% of the studied population). The GCKR
P446L gene variant was more common in patients with NAFLD than in healthy controls (86.4% vs. 50.0%, p = 0:03). Furthermore, significantly more patients with NAFLD were homozygous carriers of GCKR P446L compared to healthy controls (54.5% vs. 10.0%, p = 0:025). Both patients with histologically proven significant liver fibrosis were carriers of GCKR P446L.

In the present study we found a high prevalence of GCKR P446L polymorphism among children with NAFLD, suggesting that this gene variant is associated with development of NAFLD in the Bulgarian pediatric population. 

Author Biographies

Denitza Kofinova, Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia

Mailing Address:
Department of Pediatric Gastroenterology
and Hepatology,
University Pediatric Hospital
“Prof. Dr. Ivan Mitev”
11 Akad. Ivan Evstratiev Geshov Blvd
1606 Sofia, Bulgaria
and
Department of Pediatrics,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: kofinova@abv.bg

Iglika Yordanova, Genetic Medico-Diagnostic Laboratory Genica and Department of Medical Chemistry and Biochemistry, Medical University of Sofia

Mailing Address:
Genetic Medico-Diagnostic
Laboratory Genica
84 Ami Boue St
1612 Sofia, Bulgaria
and
Department of Medical Chemistry
and Biochemistry,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: yordanova.iglika@gmail.com

Petyo Hadzhiyski, Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia

Mailing Address:
Department of Pediatric Gastroenterology
and Hepatology,
University Pediatric Hospital
“Prof. Dr. Ivan Mitev”
11 Akad. Ivan Evstratiev Geshov Blvd
1606 Sofia, Bulgaria
and
Department of Pediatrics,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: dr.hadjiiski@abv.bg

Rayna Shentova-Eneva, Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia

Mailing Address:
Department of Pediatric Gastroenterology
and Hepatology,
University Pediatric Hospital
“Prof. Dr. Ivan Mitev”
11 Akad. Ivan Evstratiev Geshov Blvd
1606 Sofia, Bulgaria
and
Department of Pediatrics,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: rshentova@yahoo.com

Mila Baycheva, Department of Pediatric Gastroenterology and Hepatology, University Pediatric Hospital and Department of Pediatrics, Medical University of Sofia

Mailing Address:
Department of Pediatric Gastroenterology
and Hepatology,
University Pediatric Hospital
“Prof. Dr. Ivan Mitev”
11 Akad. Ivan Evstratiev Geshov Blvd
1606 Sofia, Bulgaria
and
Department of Pediatrics,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: mila.baycheva@gmail.com

Albena Todorova, Genetic Medico-Diagnostic Laboratory Genica and Department of Medical Chemistry and Biochemistry, Medical University of Sofia

Mailing Address:
Genetic Medico-Diagnostic
Laboratory Genica
84 Ami Boue St
1612 Sofia, Bulgaria
and
Department of Medical Chemistry
and Biochemistry,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: todorova_albena@abv.bg

Daniela Avdjieva-Tzavella, Department of Clinical Genetics, University Pediatric Hospital “Prof. Dr. Ivan Mitev” and Department of Pediatrics, Medical University of Sofia, Bulgaria

Mailing Address:
Department of Clinical Genetics,
University Pediatric Hospital “Prof. Dr. Ivan Mitev”
11 Akad. Ivan Evstratiev Geshov Blvd
1606 Sofia, Bulgaria
and
Department of Pediatrics,
Medical University of Sofia
15 Akad. Ivan Evstratiev Geshov Blvd
1431 Sofia, Bulgaria

E-mail: davdjieva@yahoo.com

Downloads

Published

30-06-2022

How to Cite

[1]
D. Kofinova, “Genetic Polymorphisms in Bulgarian Children with Non-alcoholic Fatty Liver Disease”, C. R. Acad. Bulg. Sci. , vol. 75, no. 6, pp. 916–922, Jun. 2022.

Issue

Section

Medicine