Molecular Analysis of HLA Genes in Romanian Patients with Chronic Hepatitis B Virus Infection

Tălăngescu, Adriana; Calenic, Bogdan; Mihăilescu, Dan Florin; Tizu, Maria; Marunțelu, Ion; Constantinescu, Alexandra E.; Constantinescu, Ileana

doi:10.3390/cimb46020067

Cited by 4 publications

(3 citation statements)

References 53 publications

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“…One of the first studies was carried out by Guja et al [ 53 ] who highlighted strong predisposing and protective associations of HLA-DQB1 in type 1 diabetes mellitus. Recently, our research group has identified HLA class I and II alleles that predispose patients to chronic renal failure [ 54 ] or increase the risk of developing hepatitis B [ 55 ]. In another work by Maruntelu et al [ 56 ], they also showed that the occurrence of celiac disease is closely associated to the HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DQB1*02:02 allele expression in Romanian patients.…”

Section: Discussionmentioning

confidence: 99%

Immunogenetic Background of Chronic Lymphoproliferative Disorders in Romanian Patients—Case Control Study

Tizu,

Calenic,

Maruntelu

et al. 2024

Medical Sciences

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Background and Objectives: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population. Materials and Methods: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP). Results: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles. Conclusions: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.

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Section: Discussionmentioning

confidence: 99%

Immunogenetic Background of Chronic Lymphoproliferative Disorders in Romanian Patients—Case Control Study

Tizu,

Calenic,

Maruntelu

et al. 2024

Medical Sciences

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“…Later, a final amplification of the size-selected library was needed to ensure proper cluster generation. Before preparing the final library, the concentration was assessed using a Qubit® fluorometer (Thermo Fisher Scientific) and adjusted in conformity with the protocol [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

“…After the NGS sequencing library was prepared using Illumina reagents, it was loaded onto an Illumina MiniSeq sequencer (Illumina, San Diego, CA, USA). After sequencing was completed, the data were interpreted using the MIA FORA NGS FLEX software (Sirona Genomics, Inc.) and two reference databases: the IMGT and Sirona Genomics databases [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

HLA Gene Polymorphisms in Romanian Patients with Chronic Lymphocytic Leukemia

Tizu,

Calenic,

Hârza

et al. 2024

Genetics Research

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Background and Objectives. Numerous genome-wide association studies have highlighted that chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with an important genetic component. An important number of genes have been implicated in CLL etiology, with some of the most important being human leukocyte antigen (HLA) genes. The aim of this study was to analyze the association of CLL with certain HLA alleles in the Romanian population and to compare our results with previous findings. Materials and Methods. This study included 66 patients with CLL, diagnosed between 2020 and 2022, and 100 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQA1/DQB1/DPA1/DPB1, and HLA-DRB1/3/4/5) were investigated using next-generation sequencing technology. Results. Several HLA alleles were strongly associated with CLL. The most important finding was that HLA-DRB1∗04:02:01 (p=0.001, OR = 1.05) and HLA-DRB3∗02:01:01 (p=0.009, OR = 1.03) have a predisposing role in CLL development. Moreover, we identified that HLA-A∗24:02:01 0.01 (p=0.01, OR = 0.38), HLA-DQA1∗05:05:01 (p=0.01, OR = 0.56), HLA-DQB1∗03:02:01 (p=0.03, OR = 0.40), and HLA-DRB4∗01:03:01 (p=0.03, OR = 0.54 alleles have protective roles. Correlations between HLA expression and gender showed that women had a higher expression of protective HLA alleles when compared to men. Conclusions. Our data are the first to indicate that in Romanian patients with CLL, the HLA-A∗24:02:01 and HLA-DQA1∗05:05:01 alleles have a protective role against CLL development, whereas HLA-DRB1∗04:02:01 and HLA-DRB3∗02:01:01alleles are positively associated with CLL.

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High Resolution HLA-A, HLA-B, and HLA-C Allele Frequencies in Romanian Hematopoietic Stem Cell Donors

Caragea,

Ursu,

Maruntelu

et al. 2024

IJMS

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The HLA genes are associated with various autoimmune pathologies, with the control of the immune response also being significant in organs and cells transplantation. The aim of the study is to identify the HLA-A, HLA-B, and HLA-C alleles frequencies in the analyzed Romanian cohort. We performed HLA typing using next-generation sequencing (NGS) in a Romanian cohort to estimate class I HLA allele frequencies up to a six-digit resolution. A total of 420 voluntary donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH) were included in the study for HLA genotyping. Peripheral blood samples were taken and brought to the Fundeni Clinical Institute during 2020–2021. HLA genotyping was performed using the Immucor Mia Fora NGS MFlex kit. A total of 109 different alleles were detected in 420 analyzed samples, out of which 31 were for HLA-A, 49 for HLA-B, and 29 for HLA-C. The most frequent HLA-A alleles were HLA-A*02:01:01 (26.11%), HLA-A*01:01:01 (12.5%), HLA-A*24:02:01 (11.67%), HLA-A*03:01:01 (9.72%), HLA-A*11:01:01, and HLA-A*32:01:01 (each with 8.6%). For the HLA-B locus, the most frequent allele was HLA-B*18:01:01 (11.25%), followed by HLA-B*51:01:01 (10.83%) and HLA-B*08:01:01 (7.78%). The most common HLA-C alleles were HLA-C*07:01:01 (17.36%), HLA-C*04:01:01 (13.47%), and HLA-C*12:03:01 (10.69%). Follow-up studies are ongoing for confirming the detected results.

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Molecular Analysis of HLA Genes in Romanian Patients with Chronic Hepatitis B Virus Infection

Cited by 4 publications

References 53 publications

Immunogenetic Background of Chronic Lymphoproliferative Disorders in Romanian Patients—Case Control Study

Immunogenetic Background of Chronic Lymphoproliferative Disorders in Romanian Patients—Case Control Study

HLA Gene Polymorphisms in Romanian Patients with Chronic Lymphocytic Leukemia

High Resolution HLA-A, HLA-B, and HLA-C Allele Frequencies in Romanian Hematopoietic Stem Cell Donors

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