Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population
| Autor: | Zane Dobele, Madara Kreile, Linda Piekuse, Zhanna Kovalova, Baiba Lace, Dmitrijs Rots |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics education.field_of_study Linkage disequilibrium business.industry Population Single-nucleotide polymorphism ARID5B General Medicine Environmental exposure CEBPE IKZF1 single nucleotide polymorphisms 03 medical and health sciences Basic Research 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Genetic predisposition childhood acute lymphoblastic leukaemia Medicine Allele business education Genetic association |
| Zdroj: | Archives of Medical Science : AMS |
| ISSN: | 1734-1922 |
| DOI: | 10.5114/aoms.2016.59920 |
| Popis: | Introduction Childhood acute lymphoblastic leukaemia (ALL) is a complex disease caused by a combination of genetic susceptibility and environmental exposure. Previous genome-wide association studies have reported several single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. Several variations in genes encoding enzymes involved in carcinogenesis are suggested as being associated with an increased risk of ALL development. Material and methods We enrolled 77 paediatric ALL patients and 122 healthy controls, and in addition parental DNA was also available for 45 probands. SNPs rs10821936 (ARID5B), rs4132601 (IKZF1), rs2239633 (CEBPE), rs3731217 (CDKN2A) and rs1800566 (NQO1) and the presence of GSTT1 and GSTM1 null variants were detected. For statistical analysis the hybrid method of two designs ‘Haplin’ was used as well as linkage disequilibrium for family-based association studies. Results We identified the SNP rs10821936 in the ARID5B gene as being statistically significantly associated with childhood ALL, especially if the C allele is in a homozygous state, relative risk (RR) 4.65, 95% CI: 2.03–10.6, p = 0.0006. Statistically significant differences were not found in other SNPs. We found risk combinations including all five variations, the strongest association being found in a combination where all five genetic variants are in a homozygous state, CCTTTTTTCC, p = 0.032. Conclusions The identified SNP rs10821936 could serve as a potential risk marker for childhood ALL development. Further studies in an independent population are needed for verification. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|