Immunogenetics最新文献

{"title":"Deciphering APOBEC1 in Avians: unravelling loss events and functional insights.","authors":"Aswin S Soman, Nagarjun Vijay","doi":"10.1007/s00251-026-01403-4","DOIUrl":"10.1007/s00251-026-01403-4","url":null,"abstract":"<p><p>In vertebrates, cytidine-to-uracil (C-to-U) editing is mediated by the AID/APOBEC family of deaminases, with APOBEC1 (A1) known to catalyse precise RNA editing of apolipoprotein B (apoB) transcripts in mammals. Despite its well-characterised role in mammals, the evolutionary history and functional divergence of A1 across birds remain underexplored. Here, we investigate the evolutionary trajectory of A1 in birds, where both the presence of the gene and apoB RNA editing activity have been questioned. Through a comprehensive in silico analysis of 81 avian genomes, we identify recurrent disruptions and catalytic inactivation of A1 in multiple lineages. Comparative sequence and structural analyses reveal a lack of domains and key residues essential for RNA binding, dimerisation, and cofactor interaction, suggesting a role in DNA editing. Furthermore, genome-wide screening for A1-associated G-to-A mutations in long terminal repeat (LTR) retrotransposons demonstrates that species with higher endogenous retrovirus (ERV) loads retain more DNA editing signatures, consistent with a defensive role of A1 against retroelements. In contrast, species with low ERV content exhibit relaxed selection and frequent A1 pseudogenisation. Together, these findings support the hypothesis that DNA editing represents the ancestral function of A1, with RNA editing in mammals evolving later as an exaptation following the expansion of A3 and changes in retroviral pressures.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allelic diversity and selection at the MHC class I and class II in a long-distance migratory shorebird, the Hudsonian Godwit (Limosa haemastica).","authors":"Kiara Fernández, Nathan R Senner, James A Johnson, Juan G Navedo, Claudio Verdugo","doi":"10.1007/s00251-026-01401-6","DOIUrl":"10.1007/s00251-026-01401-6","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) plays a central role in vertebrate adaptive immunity by encoding receptors that recognize pathogen-derived antigens. Migratory shorebirds, such as the Hudsonian Godwit (Limosa haemastica), encounter diverse pathogen landscapes across a wide range of habitats along their migratory routes. Therefore, migratory birds are expected to maintain a robust and effective immune system that minimizes the effects of infection without compromising their migration performance. We examined the genetic diversity of MHC class I exon 3 and MHC class IIB exon 2 across the species range. A total of 57 MHC-I and 13 MHC-IIB alleles were identified, with high polymorphisms observed in the peptide-binding regions (PBR). Signatures of positive selection were more pronounced in PBR sites from MHC-I than from MHC-IIB, suggesting stronger selective pressure from intracellular pathogens. In contrast, the relatively low allelic diversity and weaker selection signatures of MHC-IIB may reflect reduced exposure to extracellular pathogens. Despite broad geographic sampling, no evidence of an adaptive population structure was detected, indicating limited local adaptation and the likely influence of gene flow or neutral processes. Phylogenetic analyses revealed that some L. haemastica alleles clustered with those from closely related Scolopacidae species. These findings highlight the importance of pathogen-mediated selection in shaping MHC variation, providing valuable insights into the variability of a key group of adaptive immune genes in exceptional avian migratory species facing growing environmental pressure.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and immunological determinants of Pemphigus vulgaris: integrative analysis of HLA-DRB1 and FCGR2B variants.","authors":"Burak Kaan Kasap, Bayram Toraman, Burçin Kurt, Hande Ermis, Deniz Aksu Arıca","doi":"10.1007/s00251-026-01402-5","DOIUrl":"10.1007/s00251-026-01402-5","url":null,"abstract":"<p><p>Pemphigus vulgaris (PV) is a rare autoimmune blistering disease mediated by pathogenic autoantibodies. Although both HLA and non-HLA loci contribute to disease susceptibility, their combined roles in immune regulation remain incompletely understood. This study investigated the joint contribution of HLA-DRB1 and FCGR2B variants to PV susceptibility within an integrative immunogenetic framework. Genotype data from 286 individuals (200 controls and 86 PV patients) were analyzed using bias-reduced association models, two-locus genotype combination analyses, and cumulative genetic risk modeling. Gene-gene relationships were explored through epistasis testing, while functional relevance was examined using biological annotation approaches. HLA-DRB1*04:02 and *14:01 were significantly associated with increased PV risk, whereas *11:01 and *16:01 demonstrated protective effects after multiple testing correction (q < 0.05). The FCGR2B c.671T > C (I232T) variant showed a modest effect in single-locus analyses but did not remain statistically significant after correction for multiple testing. Several two-locus genotype combinations involving FCGR2B and HLA-DRB1 were enriched among patients; however, interaction analyses supported an additive immunogenetic architecture rather than epistasis. Genetic risk modeling demonstrated improved discrimination with weighted scores, and explainable machine-learning analysis identified HLA-DRB1 as the dominant predictor, with FCGR2B contributing a secondary modulatory signal. These findings delineate an additive immunogenetic framework underlying PV susceptibility, emphasizing the central role of HLA-DRB1. Although FCGR2B did not retain independent statistical significance after multiple-testing correction, the results suggest a potential modulatory contribution within the broader immunogenetic architecture of PV.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of gene conversion events in horse IGHV suggests preferential hotspots for diversification.","authors":"Juliana Edelvacy Lima Pinto, João Henrique Brandão Gervásio, Joseph Chi-Fung Ng, Adriano Gomes-Silva, Herbert L de Matos Guedes, Luiz Cunha, Leda R Castilho, Jerson Lima da Silva, Glória Regina Franco, Carlena Navas, Liza Figueiredo Felicori","doi":"10.1007/s00251-026-01400-7","DOIUrl":"10.1007/s00251-026-01400-7","url":null,"abstract":"<p><p>The humoral immune response relies on a diverse antibody repertoire, which is expanded through processes such as somatic hypermutation, class-switch recombination and gene conversion. These processes are primarily mediated by activation-induced cytidine deaminase (AID). Gene conversion generates diversity in immunoglobulin heavy and light chains (IGHVs) in species such as chickens and rabbits, though it has not been widely studied. Since 80% of the equine IGHV repertoire originates from only three functional gene segments, we examined gene conversion events in horses to assess their role in antibody diversification. Using a modified version of BrepConvert, which optimized analysis time, we identified gene conversion events in 6.9% of immunoglobulin sequences. The results showed a local preference, with most events occurring at the beginning of framework region 1 (FR1) and within complementarity-determining region 2 (CDR2). Pseudogenes IGHV4-35, IGHV4-53, and IGHV4-38 were utilized most frequently, while functional genes IGHV4-21, IGHV4-22, and IGHV4-29 exhibited the highest event frequencies. Interestingly, while most mismatched regions were only three nucleotides long, 91% of these events are flanked by specific sequences (six nucleotides at the 5' end and one nucleotide at the 3' end). Furthermore, functional pseudogene pairs often share identical leader regions of 5-26 nucleotides, suggesting expanded events. We also identified a potential association between these events and local non-B DNA conformations, as well as with the zinc finger protein ZNF691, which supports the involvement of DNA-binding factors. Together, these findings demonstrate that gene conversion significantly contributes to equine antibody diversity by targeting specific IGHV regions.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13183705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and evolutionary characteristics of the major histocompatibility complex class II β-chain genes of a large colony of captive king penguins (Aptenodytes patagonicus).","authors":"Reona Dei, Yukie Miyazawa, Natsumi Ota, Hiroki Narashima, Eri Kikkawa, Shingo Suzuki, Atsuko Shigenari, Sayaka Ito, Tomi T Tsuda, Jerzy K Kulski, Takashi Shiina, Yuki F Kita","doi":"10.1007/s00251-026-01398-y","DOIUrl":"10.1007/s00251-026-01398-y","url":null,"abstract":"<p><p>Major histocompatibility complex class II beta (MHC-class IIB) genes are highly polymorphic and play important roles in immune function, making them valuable DNA markers for efficient animal breeding and conservation management programs. However, MHC genetic information on king penguins (Aptenodytes patagonicus; Appa) in captivity remains limited. Here, we developed a Next Generation Sequencing (NGS)-based genotyping method to characterize MHC class IIB (Appa-CIIB) polymorphisms in 99 king penguins housed at Adventure World (Wakayama, Japan), identifying 72 novel Appa-CIIB alleles, each encoding a distinct amino acid sequence. Phylogenetic analysis classified these alleles into two major and one minor lineage, with peptide-binding regions in the main lineages showing signatures of positive selection. Thirty-four Appa-CIIB haplotypes composed of one to three Appa-CIIB loci, were inferred using individual management records (IMRs) from 123 individuals. Pedigree analysis revealed that 114 individuals belonged to a single extended family encompassing up to five generations, with the founders representing the first generation. Despite over 30 years of captive maintenance, population genetic analyses indicated that this population has retained high genetic diversity. The identification of multiple Appa-CIIB loci and copy number variations suggests that the Appa-CIIB region has undergone gene duplication and recombination events during evolution. These findings provide valuable insights into the genetics and evolutionary characteristics of Appa-CIIB genes and offer a practical framework for managing king penguin gene diversity in captivity, supporting future breeding programs that minimize inbreeding depression and maintain healthy populations.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The digital keystone: how artificial intelligence is reshaping HLA research and clinical practice.","authors":"Gamze Sonmez, Yigit Yazarkan, Deniz Cagdas","doi":"10.1007/s00251-026-01397-z","DOIUrl":"10.1007/s00251-026-01397-z","url":null,"abstract":"<p><p>The human leukocyte antigen (HLA) system underpins allorecognition and shapes the response to infection, autoimmunity, and treatment response. Technological advances from serology to next-generation sequencing now enable full-gene characterization and four-field HLA nomenclature, while artificial intelligence (AI) and machine learning are transforming the data generation, interpretation, and clinical use. This review summarizes the progress on the technical developments in the HLA era, which could be evaluated in three perspectives. First, we survey AI for antigen processing and T-cell recognition, including HLA–peptide binding, presentation, and T cell receptor (TCR)–epitope models, and outline their effects on applications like neoantigen discovery, vaccine design, and tolerance induction. Since there are still persistent gaps in immunogenicity prediction and coverage of rare alleles, secondly, we evaluated HLA imputation from the single nucleotide polymorphism (SNP) arrays and low-coverage whole-genome sequencing, highlighting deep learning models that improve accuracy for common and low-frequency alleles, and the critical role of diverse reference panels. Third, we assessed the AI-enabled transplant decision support: survival and graft-versus-host disease forecasting from registry data, donor ranking beyond simple allele match, and crossmatch compatibility prediction. We integrate emerging biology, non-classical HLA molecules, allele-specific expression, and HLA loss of heterozygosity, as key modulators of immune activation and evasion with implications for donor selection, infectious diseases, vaccinology, inflammatory disease, and cancer therapy. To accelerate safe clinical translation, we need to have standards for data governance, fairness auditing, validation and calibration, explainability, robustness, monitoring, and human oversight. By bridging core HLA principles with recent biological insights and AI innovations, we outline a path toward reproducible and equitable clinical translation to immunogenomics in transplantation, infectious, inflammatory, oncologic diseases, and precision vaccinology.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of CCR1 and CCR1L1 reveals complex duplication scenarios in Muroids and Ruminants.","authors":"João Pedro Marques, Ana Pinheiro, Pedro José Esteves","doi":"10.1007/s00251-026-01399-x","DOIUrl":"10.1007/s00251-026-01399-x","url":null,"abstract":"<p><p>Chemokine receptor type 1 (CCR1) is expressed on several immune cells, including neutrophils, monocytes, and T cells. In rodents, a paralog of CCR1 was identified and called CCR1L1. Here, we studied the evolution of the CCR1 gene in mammals. Our results show that CCR1L1 is restricted to specific mammalian lineages, with muroids and ruminants each harbouring two CCR1-related paralogs. Topology tests do not unambiguously discriminate between independent duplications and an ancestral duplication followed by lineage-specific losses. Branch-site analyses revealed episodic positive selection acting on CCR1L1 lineages, including the basal branches of the two CCR1L1 clades. Moreover, we observed that selective regimes differ between the two CCR1L1 mammalian groups, with evidence for a shift in selection intensity in ruminants but not in muroids. We identified several amino acid changes in the structural components of chemokine receptors that are likely to impact the Ruminants CCR1L1 function. In Bos javanicus and Moschus berezovskii, CCR1L1 pseudogenes with premature stop codons were identified. Expression data indicate that Bos taurus, CCR1 is expressed in at least seven tissues, whereas CCR1L1 is only expressed in the lung. Together, these results suggest a complex evolutionary history for CCR1L1, involving duplication, lineage-specific selection, and, in some species, pseudogenization.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the genetic control of immune cell function at single-cell resolution: Disease-Specific Cis-eQTLs analysis of COVID-19.","authors":"E I Romanova, D I Tychinin, A M Shaymardanov, V E Akimov, A V Korobeinikova, V V Shiryagin, N I Guskova, V A Astafieva, A S Shingaliev, O A Antonova, L A Golubnikova, S I Mitrofanov, K S Grammatikati, V S Yudin, S M Yudin, A V Makhotenko, A A Keskinov, S A Kraevoy, E A Snigir, P Yu Volchkov, D V Svetlichnyy, V I Skvortsova","doi":"10.1007/s00251-026-01396-0","DOIUrl":"10.1007/s00251-026-01396-0","url":null,"abstract":"<p><p>Integrating whole-genome sequencing with single-cell RNA-seq data enhances the current understanding of how genomic differences across humans contribute to variations in gene activity. eQTL discovery offers a potent method for decoding genomic regulation and identifying population-specific genomic variants associated with gene expression differences. The current development of single-cell sequencing technologies provides a significant opportunity for precise and detailed profiling of both major and minor cell states, facilitating the identification of genomic variants and their effects within specific cellular contexts. Therefore, this study aims to investigate the combined analysis of paired whole-genome and single-cell RNA-seq data from 230,000 peripheral blood mononuclear cells (PBMCs) across 30 individuals. Overall, 1,233,644 cis-eQTLs were identified across 18 cell types in PBMCs. The results were thoroughly evaluated through conservation analysis, revealing that the most statistically significant eQTLs are associated with less conserved genomic regions and are concentrated in the regulatory areas of more divergent genes. Using deep learning-based cis-regulatory models, cis-eQTLs were further investigated to reveal the cell-type-specific context of variant activity. The analysis revealed how eQTLs influence the expression of key immune-related genes (NKG7, HLA, MIF, MS4A1), identifying transcription factors whose binding sites are disrupted by genomic variants. This study integrates genetics, single-cell transcriptomics, and deep learning models to reveal and understand the role of genomic variants in gene expression regulation.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Class switched bovine ultralong CDR H3 amplicons versus canonical in immune and non-immune tissues.","authors":"Karina L Hissen, Morgan Sheppard, Jeannine A Ott, Kerstin K Landrock, Casey Whitley, Nicholas Ebert, J M Cody Horton, Nicole A Glenn, Yoonsung Jung, Vaughn V Smider, Michael F Criscitiello","doi":"10.1007/s00251-026-01395-1","DOIUrl":"10.1007/s00251-026-01395-1","url":null,"abstract":"<p><p>Within the bovine immune response, a distinct type of immunoglobulin (Ig), known as ultralong complementarity-determining region 3 (CDR3) antibodies, coexists alongside canonical Igs. These ultralong heavy chains (HC) feature a remarkable structure with a lengthened CDR3 of the heavy chain (CDR H3), allowing them to adopt either a smaller and more extended paratope than canonical antibodies. However, very little is known about the distribution of ultralong CDR H3s in cattle tissues and which isotypes they are ultimately associated with. This study analyzed and quantified the amplicons of the five immunoglobulin isotypes (IgM, IgD, IgG, IgA, and IgE) for both the canonical and ultralong CDR H3 throughout 24 Bos taurus tissues. IgH amplicons analysis identified an extensive repertoire of expressed canonical and ultralong CDR H3s of each isotype in most tissues. Ultralong cattle Igs were preferentially switched to the IgG isotype, especially in the medial retropharyngeal lymph node draining the immunization site. Additionally, B cells producing canonical Igs in bone marrow switched most to the IgG isotype. These data suggest that ultralong CDR H3 may be uniquely qualified to handle some antigens. A more comprehensive understanding of isotype and tissue-specific immune responses of these unusual antibodies can provide a deeper insight into their function within the overall cattle immune system, offering unique opportunities for innovations for in both bovine health and human immunotherapeutics.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKG2D genetic variants and cancer susceptibility: Integrating case-control evidence with meta-analysis.","authors":"Nguyen Hoang Viet, Le Thanh Dong, Do Tung Dac, Hai Ha Long Le, Le Thi Phuong, Pham Phuong Thao, Hoang Thao Giang Nguyen, J Luis Espinoza","doi":"10.1007/s00251-025-01393-9","DOIUrl":"10.1007/s00251-025-01393-9","url":null,"abstract":"<p><p>Lymphomas are biologically heterogeneous malignancies with multifactorial etiologies involving genetic, environmental, and immune dysregulation. The functional variant rs1049174 SNP in the KLRK1 gene (encoding NKG2D) regulates NKG2D expression and modulates NK cells immune surveillance pathways, which may influence lymphoma susceptibility. We investigated this association through a two-stage case-control study and meta-analysis. First, we analyzed 246 diffuse large B-cell lymphoma (DLBCL) patients and 599 healthy controls (exploratory cohort), followed by a confirmatory cohort of 234 non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma (HL) patients. Genotype frequencies were assessed via chi-square tests, with odds ratios (ORs) calculated for risk associations. A systematic review and meta-analysis of 10 studies, including our cohorts (3,785 cases and 4,129 controls), testing rs1049174 and cancer risk was also conducted. In the exploratory cohort, the GG genotype showed no significant association with overall lymphoma risk (OR = 0.83; 95% CI: 0.61-1.13; *p* = 0.25). However, in NHL, the GG genotype was underrepresented (OR = 0.75; 95% CI: 0.57-0.99; *p* = 0.02). Pooled lymphoma analysis revealed a protective effect (OR = 0.78; 95% CI: 0.62-0.99; *p* = 0.03). Meta-analysis confirmed a significant protective role of the GG genotype against cancer (OR = 0.71; 95% CI: 0.63-0.79), despite heterogeneity and potential publication bias. Our findings suggest that the rs1049174 GG genotype is associated with reduced lymphoma susceptibility, particularly in NHL, underscoring the importance of immunogenetic variants in lymphomagenesis. Further functional and clinical studies are needed to elucidate the mechanistic basis of this association.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"78 1","pages":"2"},"PeriodicalIF":2.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}