High incidence of rare TGFB1 haplotypes in children with biliary atresia
Objective: to evaluate the occurrence of single nucleotide polymorphisms (SNPs) in transforming growth factor beta 1 (TGFB1) – rs1800469, rs1800470, rs1800471 – and their haplotypes in children with biliary atresia (BA).Materials and methods. We studied 106 pediatric liver recipients aged 4 to 150 (...
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Federal Research Center of Transplantology and Artificial Organs named after V.I.Shumakov
2024-09-01
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| Series: | Вестник трансплантологии и искусственных органов |
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| Online Access: | https://journal.transpl.ru/vtio/article/view/1840 |
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| author | R. M. Kurabekova O. E. Gichkun O. M. Tsirulnikova I. E. Pashkova E. A. Vakurova O. P. Shevchenko S. V. Gautier |
| author_facet | R. M. Kurabekova O. E. Gichkun O. M. Tsirulnikova I. E. Pashkova E. A. Vakurova O. P. Shevchenko S. V. Gautier |
| author_sort | R. M. Kurabekova |
| collection | DOAJ |
| description | Objective: to evaluate the occurrence of single nucleotide polymorphisms (SNPs) in transforming growth factor beta 1 (TGFB1) – rs1800469, rs1800470, rs1800471 – and their haplotypes in children with biliary atresia (BA).Materials and methods. We studied 106 pediatric liver recipients aged 4 to 150 (median 8) months, of whom 44 were boys, and 199 healthy individuals aged 32.7 ± 9.6 years, of whom 79 were boys. The indication for pediatric liver transplantation was BA. Genomic DNA was isolated from peripheral blood using a commercial QIAamp DNA Blood Mini Kit on a QIAcube automated analyzer. SNPs rs1800469, rs1800470, and rs1800471 in the TGFB1 gene were determined by real-time polymerase chain reaction using TaqMan probes on a CFX96 amplifier.Results. In children with BA, the occurrence of the investigated SNPs in TGFB1 was as follows: rs1800469 – 38% GG homozygotes, 50% AG heterozygotes and 12% AA homozygotes; rs1800470 – 39% AA, 44% AG, 17% GG; rs1800471 – 88% CC, 12% GC, 0% GG. The distributions of all the three SNPs followed the Hardy–Weinberg principle. For rs1800469 and rs1800470, the genotype and allele frequencies in children with BA did not differ from those in healthy individuals, whereas for rs1800471, the heterozygous GC genotype was three-fold more frequent in children with BA than in healthy individuals. Haplotype analysis showed the presence of 6 major combinations: 2 most frequent were present in a total of about 66% of patients and 91% of healthy individuals, each of the frequencies practically did not differ between the comparison groups. Significant differences were found in the frequency of 3 rarer haplotypes, A-A-C, G-G-C and G-A-G at position rs1800469, rs1800470, rs1800471, which were observed more frequently in patients with BA by 3.10 (CI 1.59 to 6.04) (p = 0.001), 3.10 (CI 1.55 to 6.17) (p = 0.0015), and 17.02 (CI 1.94 to 149.30) (p = 0.011) times, respectively, than in healthy individuals.Conclusion. In children with BA, the occurrence of CG heterozygotes in rs1800471 and the distribution of three rare haplotypes A-A-C, G-G-C and G-A-G of the rs1800469, rs1800470 and rs1800471 SNPs in the TGFB1 gene significantly differs from that in healthy individuals. It is possible that carriage of rare genotypes and haplotypes of TGFB1 may predispose to BA in children. |
| format | Article |
| id | doaj-art-ff796dccbc324299b50a2c6f4ec32d65 |
| institution | Kabale University |
| issn | 1995-1191 |
| language | Russian |
| publishDate | 2024-09-01 |
| publisher | Federal Research Center of Transplantology and Artificial Organs named after V.I.Shumakov |
| record_format | Article |
| series | Вестник трансплантологии и искусственных органов |
| spelling | doaj-art-ff796dccbc324299b50a2c6f4ec32d652025-08-20T03:38:19ZrusFederal Research Center of Transplantology and Artificial Organs named after V.I.ShumakovВестник трансплантологии и искусственных органов1995-11912024-09-0126316817510.15825/1995-1191-2024-3-168-1751290High incidence of rare TGFB1 haplotypes in children with biliary atresiaR. M. Kurabekova0O. E. Gichkun1O. M. Tsirulnikova2I. E. Pashkova3E. A. Vakurova4O. P. Shevchenko5S. V. Gautier6Shumakov National Medical Research Center of Transplantology and Artificial OrgansShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityShumakov National Medical Research Center of Transplantology and Artificial OrgansSechenov UniversityShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityObjective: to evaluate the occurrence of single nucleotide polymorphisms (SNPs) in transforming growth factor beta 1 (TGFB1) – rs1800469, rs1800470, rs1800471 – and their haplotypes in children with biliary atresia (BA).Materials and methods. We studied 106 pediatric liver recipients aged 4 to 150 (median 8) months, of whom 44 were boys, and 199 healthy individuals aged 32.7 ± 9.6 years, of whom 79 were boys. The indication for pediatric liver transplantation was BA. Genomic DNA was isolated from peripheral blood using a commercial QIAamp DNA Blood Mini Kit on a QIAcube automated analyzer. SNPs rs1800469, rs1800470, and rs1800471 in the TGFB1 gene were determined by real-time polymerase chain reaction using TaqMan probes on a CFX96 amplifier.Results. In children with BA, the occurrence of the investigated SNPs in TGFB1 was as follows: rs1800469 – 38% GG homozygotes, 50% AG heterozygotes and 12% AA homozygotes; rs1800470 – 39% AA, 44% AG, 17% GG; rs1800471 – 88% CC, 12% GC, 0% GG. The distributions of all the three SNPs followed the Hardy–Weinberg principle. For rs1800469 and rs1800470, the genotype and allele frequencies in children with BA did not differ from those in healthy individuals, whereas for rs1800471, the heterozygous GC genotype was three-fold more frequent in children with BA than in healthy individuals. Haplotype analysis showed the presence of 6 major combinations: 2 most frequent were present in a total of about 66% of patients and 91% of healthy individuals, each of the frequencies practically did not differ between the comparison groups. Significant differences were found in the frequency of 3 rarer haplotypes, A-A-C, G-G-C and G-A-G at position rs1800469, rs1800470, rs1800471, which were observed more frequently in patients with BA by 3.10 (CI 1.59 to 6.04) (p = 0.001), 3.10 (CI 1.55 to 6.17) (p = 0.0015), and 17.02 (CI 1.94 to 149.30) (p = 0.011) times, respectively, than in healthy individuals.Conclusion. In children with BA, the occurrence of CG heterozygotes in rs1800471 and the distribution of three rare haplotypes A-A-C, G-G-C and G-A-G of the rs1800469, rs1800470 and rs1800471 SNPs in the TGFB1 gene significantly differs from that in healthy individuals. It is possible that carriage of rare genotypes and haplotypes of TGFB1 may predispose to BA in children.https://journal.transpl.ru/vtio/article/view/1840congenital and hereditary liver diseasesbiliary atresiapediatric liver recipientsliver transplantationrs1800469rs1800470rs1800471polymorphism |
| spellingShingle | R. M. Kurabekova O. E. Gichkun O. M. Tsirulnikova I. E. Pashkova E. A. Vakurova O. P. Shevchenko S. V. Gautier High incidence of rare TGFB1 haplotypes in children with biliary atresia Вестник трансплантологии и искусственных органов congenital and hereditary liver diseases biliary atresia pediatric liver recipients liver transplantation rs1800469 rs1800470 rs1800471 polymorphism |
| title | High incidence of rare TGFB1 haplotypes in children with biliary atresia |
| title_full | High incidence of rare TGFB1 haplotypes in children with biliary atresia |
| title_fullStr | High incidence of rare TGFB1 haplotypes in children with biliary atresia |
| title_full_unstemmed | High incidence of rare TGFB1 haplotypes in children with biliary atresia |
| title_short | High incidence of rare TGFB1 haplotypes in children with biliary atresia |
| title_sort | high incidence of rare tgfb1 haplotypes in children with biliary atresia |
| topic | congenital and hereditary liver diseases biliary atresia pediatric liver recipients liver transplantation rs1800469 rs1800470 rs1800471 polymorphism |
| url | https://journal.transpl.ru/vtio/article/view/1840 |
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