Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population

Publisher Copyright: Copyright © 2016 Termedia & Banach.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.publishersversionPeer reviewe

Natural clearance of hepatitis C virus in hemophilia patients

Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Objective. The objective of this study was to investigate the prevalence of HCV (hepatitis C virus) infection in hemophilia patients in Latvia and to analyze association between natural clearance of HCV and human leukocyte antigen (HLA) class II genes. Material and methods. From 61 hemophilic patients participating in this study, 38 were adults and 23 were pediatric patients younger than 18 years. To analyze association between HLA class II alleles and natural clearance of HCV, the gene frequency was compared in hemophilia patients group and the control group of 60 healthy subjects, all men. Serum HCV RNA was qualitatively determined and HLA class II alleles were identified by polymerase chain reaction (PCR) method. Results. HCV infection is common among hemophilia patients in Latvia. Antibodies to HCV were found in 45 of 61 (74%) hemophilia patients. In 41% of hemophilia patients (18 of 44), HCV infection resolved spontaneously. Children cleared HCV more frequently than adults (7 of 11 comparing to 11 of 33, respectively; OR=3.50; P<0.05). The frequency difference was found to be statistically significant when comparing HLA alleles distribution in the sample of hemophilia patients who naturally cleared HCV (n=18) and in the control group (n=60) (corresponding frequency of HLA-DRB1*07 allele - 4 (11.11%) and 9 (1.67%); OR=7.38; P<0.05). Conclusions. Natural clearance of HCV infection is frequently found in hemophilia patients in Latvia. Children are more likely to clear virus naturally than adults. There is an association between natural clearance of HCV and HLA allele DRB1*07 in hemophilia patients.Peer reviewe

Lack of association between polymorphisms in genes MTHFR and MDR1 with risk of childhood acute lymphoblastic leukemia

Background: Acute lymphoblastic leukemia (ALL) is a complex disease caused by interactions between hazardous exogenous or/and endogenous agents and many mild effect inherited susceptibility mutations. Some of them are known, but their functional roles still requireinvestigation. Age is a recognized risk factor; children with disease onset after the age of ten have worse prognosis, presumably also triggered by inherited factors. Materials and Methods: The MDR1 gene polymorphisms rs1045642, rs2032582 and MTHFR gene polymorphisms rs1801131 and rs1801133 were genotyped in 68 ALL patients in remission and 102 age and gender matched controls; parental DNA samples were also available for 42 probands. Results: No case control association was found between analyzed polymorphisms and a risk of childhood ALL development. Linkage disequilibrium was not observed in a family-based association study either. Only marginal association was observed between genetic marker rs2032582A and later disease onset (p=0.04). Conclusions: Our data suggest that late age of ALL onset could be triggered by mild effect common alleles.publishersversionPeer reviewe

X-Linked Lymphoproliferative Disease in Latvia: A Report of Two Clinically Distinct Cases

X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency. Affected individuals usually present with the Epstein–Barr virus infection and have no apparent disease prior to presentation. The most common clinical manifestations are fulminant infectious mononucleosis, dysgammaglobulinaemia, and lymphoma (usually of B-cell origin). XLP is caused by mutations in the SH2D1A gene which encodes the intracellular adaptor molecule SAP (signalling lymphocyte activation molecule- (SLAM-) associated protein). SAP is predominantly expressed in T cells and NK cells and functions to regulate signal transduction pathways downstream of the SLAM family of surface receptors to control CD4+ T cell (and by extension B-cell), CD8+ T cell and NK cell function, and development of NKT cells. Thus, SAP mutations cause dysregulation of the immune system, with defects in both cellular and humoral immunity. Here we report two clinical cases of three patients who presented with different manifestations of XLP, namely, fulminant infectious mononucleosis, Burkitt lymphoma and hypogammaglobulinaemia

Supportive care in pediatric acute myeloid leukemia : expert-based recommendations of the NOPHO-DB-SHIP consortium

Introduction Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. Area covered The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. Expert opinion Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome