International Journal of Immunogenetics最新文献

This meta-analysis aims to evaluate the association between interleukin-10 (IL-10) -819 C/T (rs1800871), -592 C/A (rs1800872) and -1082 A/G (rs1800896) polymorphisms and leprosy susceptibility by analyzing multiple genetic models in the Asian and Caucasian populations. A systematic literature search was conducted in PubMed, Web of Science, Google Scholar and Embase (January 2001 to February 2025) following PRISMA guidelines. Case-control studies reporting genotype distributions for IL-10 polymorphisms in leprosy cases and controls were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under allelic, recessive, dominant and over-dominant models. Heterogeneity was assessed using Cochran's Q test and the I² statistic. Publication bias was evaluated using Egger's test and funnel plots. A total of 13 studies were included, comprising 5509 leprosy cases and 8135 controls. The -1082 A/G variant exhibited a significant protective effect across allelic (A vs. G OR = 0.73, 95% CI 0.59-0.91, p = 0.005), dominant (AA+AG vs. GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006) and the over-dominant models (AG vs. AA+ GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006). Under the dominant model, the -819 C/T (CC+CT vs. TT OR = 0.76, 95% CI 0.61-0.96, p = 0.02) and -592 C/A (CC+CA vs. AA OR = 0.71, 95% CI 0.52-0.97, p = 0.03) polymorphisms also showed significant protective effects, suggesting a potential role of heterozygosity in reducing leprosy susceptibility. Subgroup analysis indicated stronger protective effects in Asians. Power analysis confirmed that the included studies had sufficient sample sizes to detect significant associations (α error probability < 0.05). This meta-analysis supports the protective role of IL-10 polymorphisms, particularly the -1082 A (rs1800896) allele, in reducing leprosy susceptibility. These findings underscore the role of genetic variation in disease susceptibility and suggest that IL-10 polymorphisms could serve as biomarkers for leprosy susceptibility.

Preeclampsia (PE) is a major pregnancy complication with considerable maternal and fetal morbidities. The recent evidence indicates that immunological factors have critical roles in PE pathogenesis. This study assessed the association between genetic variations in IL-35 components, specifically IL-12A (rs568408) and EBI3 (rs4740) polymorphisms, and PE susceptibility in an Iranian population. A case-control study with 470 participants was carried out, and polymorphism detection was achieved by the PCR-RFLP technique. Genetic analysis revealed distinct associations between IL-35 components polymorphisms and PE risk. For IL-12A rs568408, the AA mutant genotype significantly increased PE susceptibility (OR = 3.350, p = 0.007), with stronger associations in severe PE cases (OR = 5.048, p < 0.001). Similarly, the mutant allele showed risky effects in total group and severe subgroup (OR = 1.743, p = 0.001; OR = 2.307, p < 0.001). The EBI3 rs4740 polymorphism analysis showed that AA genotype carriers had a protective effect (OR = 0.495, p = 0.036), particularly noticeable in severe cases (OR = 0.409, p = 0.037). In addition, the mutant allele demonstrated protective effects in the total PE, severe and particularly in early-onset manifestations (OR = 0.651, OR = 0.559, OR = 0.478, respectively). Combined genotype analysis showed that IL-12A AA/EBI3 GA carriers had the highest risk of severe, early-onset PE (OR = 5.280, p = 0.046, OR = 5.945, p = 0.038). This study provides a better understanding of the causes of PE and points out possible genetic markers to be used in its risk assessment.

Background/objectives: The human major histocompatibility complex (MHC) is characterized by extreme polymorphism, with HLA-C contributing to pathogen defence, disease susceptibility, and transplantation outcomes. Beyond allelic diversity, and variation, the evolutionary restructuring of haplotypes influences functional diversity across the region. This study analysed HLA-C haplotypes in the context of transposable element (TE) architecture and single-nucleotide polymorphism (SNP) patterns to identify conserved modules and ancestral recombination boundaries.

Methods: Paired genomic alignments of fully phased homozygous lymphoblastoid cell lines carrying 36 haplotypes of HLA-C*01-C*07, C*12, and C*16 allelic groups were performed using Mauve to define locally co-linear blocks. SNP density plots were generated to visualize transitions between SNP-rich and SNP-poor regions. Six diverse HLA-C*07 haplotypes (linked to HLA-B*07, *08, *18, *49, *57 and *58) were examined as a primary case study. Particular focus was placed on crossover zones where SNP transitions coincided with TE boundaries, indicating putative ancestral recombination breakpoints.

Results: Comparative analyses revealed extensive structural variation among C*07 haplotypes and across the broader C*01-C*16 series. The C*07:02 homologs exhibited significantly higher SNP density (mean = 1.87 ± 0.44 SNPs/kb, n = 10) than C*07:01 and C*07:18 homologs (mean = 0.29 ± 0.21 SNPs/kb, n = 20; p < 0.001). Abrupt SNP transitions frequently aligned with SINE, LINE, and LTR elements (e.g., Alu, L1, L2, HERV), marking recurrent TE-associated junctions. These breakpoints defined shared homozygous HLA-C segments spanning ∼4 kb to ∼4 Mb, consistent with mosaic haplotype evolution through recombination of conserved modules.

Conclusions: HLA-C haplotypes exhibit modular mosaic structures shaped by recurrent recombination at TE-associated crossover zones. Thus, MHC haplotypes may share the same HLA-C allele, yet differ in the surrounding HLA-B and class I genomic organization, preserving or disrupting co-adapted functional units. Incorporating haplotypic mosaicism, rather than focusing solely on allelic polymorphism, may improve models of immune variation, disease risk, and translation matching.

Familial cold autoinflammatory syndrome 2 is a rare autoinflammatory disorder caused by mutations in the NLRP12 gene, characterized by recurrent fever, arthralgia and rash triggered by cold exposure. This case report presents a 9-year-old boy with intellectual disability, microcephaly and skin lesions, where genetic testing revealed heterozygous pathogenic variants in both KIF11 (NM_004523.4:c.2304_2305del) and NLRP12 (NM_144687.4:c.770del) genes. While the KIF11 variant has been previously documented, the NLRP12 variant is novel and classified as likely pathogenic. This study also includes a systematic review analysing 28 studies and 100 patients with NLRP12 mutations, revealing a phenotypic spectrum ranging from classic symptoms like fever and rash to rarer features such as hypogonadism, hypothyroidism and neurological abnormalities. A significant concentration of variants was noted in Exon 3 of NLRP12, but no clear genotype-phenotype correlation was established. These findings underscore the utility of next-generation sequencing in diagnosing rare genetic conditions, particularly in patients presenting with seemingly minor symptoms. The coexistence of mutations in KIF11 and NLRP12 highlights potential interactions between distinct genetic pathways, emphasizing the need for further research. Including NLRP12 in diagnostic panels and updating databases like the Human Phenotype Ontology are crucial for improving diagnosis, understanding phenotypic diversity and optimizing patient management.