Association between Killer Immunoglobulin-like receptor genes and susceptibility to inflammatory bowel disease: An updated meta-analysis
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ABSTRACT:
SUBMITTER: Ponce G
PROVIDER: S-EPMC11296034 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:Genetic studies have illustrated that killer cell immunoglobulin-like receptor (KIR) genes could participate in various autoimmune disorders. We aimed to clarify the role of KIR genes, HLA ligands, HLA-KIR interactions, and their genotypes in inflammatory bowel disease (IBD) susceptibility. The study population was composed of 183 IBD subjects, comprising 100 ulcerative colitis (UC) patients, 83 Crohn's disease (CD) patients, and 274 healthy subjects. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to evaluate the absence or presence of the 15 KIR genes, 5 HLA class I ligands, and 2 pseudogenes. We did not find any significant difference in allele frequency of KIRs and pseudogenes between IBD patients and healthy controls. In the case of HLA genes, there was a significant difference in HLA-B-Bw4Thr80 frequency between UC patients and healthy controls (P = 0.03, OR = 0.06, 95%CI = 0.008-0.4). Furthermore, we found a significant difference in HLA-C1Asn80 frequency between CD patients and healthy controls (P = 0.04, OR = 0.49, 95% CI = 0.3-0.8). In the full-array combination of KIR genes, there was no significant frequency difference between UC patients and healthy controls, while two KIR genotypes showed a significant susceptible association with CD. Our data do not support a strong role of NK cells in IBD susceptibility, but it does not rule out a role for KIR variability in IBD patients. However, there are some protective associations such as Bw4 alleles; these associations may be due to the interaction of the alleles to TCRs rather than KIRs.
| S-EPMC7520679 | biostudies-literature
Project description:ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR) on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class І genes as their corresponding ligands in RA patients and control subjects.MethodsIn this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR). Differences in the frequency of genes and haplotypes were determined by χ² test.ResultsKIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56) to a powerful predisposition to RA (OR = 16.47). Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA.ConclusionIndividuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.
| S-EPMC4687638 | biostudies-literature
Project description:The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility genes in complex diseases has involved genome wide linkage studies followed by studies of positional candidate genes in loci of interest. This review encompasses data from studies into novel candidate genes implicated in the pathogenesis of inflammatory bowel disease. Novel techniques to identify candidate genes-genome wide association studies, yeast-two hybrid screening, microarray gene expression studies and proteomic profiling, are also reviewed and their potential role in unravelling the pathogenesis of inflammatory bowel disease are discussed.
| S-EPMC4087674 | biostudies-literature
Project description:The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.
| S-EPMC9877653 | biostudies-literature
Project description:PurposeThe -1237T/C polymorphism of the Toll-like receptor 9 (TLR9) gene has been implicated in the susceptibility of inflammatory bowel diseases (IBDs), but the results remain conflicting. We further investigated this association via meta-analysis.Materials and methodsMultiple electronic databases were extensively searched until February, 2015. The strength of association was evaluated by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 2987 cases and 2388 controls from eight studies were analyzed. Overall, association was found between TLR9 -1237T/C polymorphism and the risk of IBDs when all the studies were pooled (recessive model, OR: 1.59, 95% CI: 1.02-2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04-2.52, p=0.03; allele model, OR: 1.13, 95% CI: 1.00-1.27, p=0.05). Stratification by ethnicity indicated an association between TLR9 -1237T/C polymorphism and IBDs risk in Caucasians (recessive model, OR: 1.59, 95% CI: 1.02-2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04-2.52, p=0.03; allele model, OR: 1.12, 95% CI: 1.00-1.27, p=0.05). When stratified by disease type, significant correlation were only found in the Crohn's disease subgroup (recessive model, OR: 1.69, 95% CI: 1.05-2.73, p=0.03; homozygote model, OR: 1.74, 95% CI: 1.07-2.82, p=0.02; allele model, OR: 1.15, 95% CI: 1.01-1.32, p=0.04).ConclusionThe present study suggested that the TLR9 -1237T/C polymorphism might act as a risk factor in the development of IBDs, particularly in Caucasians.
| S-EPMC4696948 | biostudies-literature
Project description:Natural killer cells (NK cells) play a major role in the immune response to cancer. An important element of NK target recognition is the binding of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Colorectal carcinoma (CRC) is one of the most common types of inflammation-based cancer. The purpose of the present study was to investigate the presence of KIR genes and HLA class I and II alleles in 1074 CRC patients and 1272 controls. We imputed data from single-nucleotide polymorphism (SNP) Illumina OncoArray to identify associations at HLA (HLA-A, B, C, DPB1, DQA1, DQB1, and DRB1) and KIRs (HIBAG and KIR*IMP, respectively). For association analysis, we used PLINK (v1.9), the PyHLA software, and R version 3.4.0. Only three SNP markers showed suggestive associations (p < 10-3; rs16896742, rs28367832, and rs9277952). The frequency of KIR2DS3 was significantly increased in the CRC patients compared to healthy controls (p < 0.005). Our results suggest that the implication of NK cells in CRC may not act through allele combinations in KIR and HLA genes. Much larger studies in ethnically homogeneous populations are needed to rule out the possible role of allelic combinations in KIR and HLA genes in CRC risk.
| S-EPMC7072752 | biostudies-literature
Project description:BackgroundGrowing evidence suggests that inflammatory bowel disease (IBD) and dementia share pathological mechanisms and pathogenic risk factors. However, the previously diagnosed IBD and the subsequent risk of developing dementia are largely unknown.AimThe purpose of this review is to assess the association between IBD and subsequent dementia diagnosis.MethodsWe searched PubMed, Embase, and Cochrane library from database inception to February 1, 2022. Two reviewers independently extracted data and assessed methodological quality and risk of bias. Observational study that reported the possibility of dementia in IBD and non-IBD populations were included. Eligible studies were pooled effect estimates for relative risk (RR) through fixed-or random-effects models as appropriate.ResultsMore than 3,181,549 participants from nine studies met the inclusion criteria. Previous IBD diagnosis did not increased the risk of subsequent all-cause dementia (RR, 1.32; 95% CI, 0.98-1.77) and AD-dementia (RR, 1.62; 95% CI, 0.96-2.76). Subgroup analyses based on study design indicated that cohort studies (RR, 1.30; 95% CI, 1.09-1.55) reported an increased risk of all-cause dementia, but were not applicable to AD-dementia (RR, 1.27; 95% CI, 0.94-1.72). Positive associations between IBD patients and all-cause dementia did not differ by age and gender in cohort studies. Both ulcerative colitis (UC) (RR, 1.39; 95% CI, 1.00-1.94) and Crohn's disease (RR, 1.46; 95% CI, 1.08-1.98) are associated with increased risk of all-cause dementia.ConclusionEvidence regarding dementia risk assessment in IBD patients is conflicting, which may be influenced by study design. More prospective cohort studies are needed to determine their relationship.Systematic review registration[https://www.prosper-isd.net], identifier [CRD42021284116].
| S-EPMC9581261 | biostudies-literature
Project description:BackgroundChronic systemic inflammation may be associated with neurocognitive decline, but the relationships between inflammatory bowel disease and related medications and the risk of Alzheimer's disease remain unclear.MethodsWe performed a meta-analysis to evaluate the associations of ulcerative colitis, Crohn's disease and related medications with risk of Alzheimer's disease. We identified cohort and case-control studies by searching PubMed, Embase and Web of Science up to August 2022.ResultsSeven eligible studies with 20,174 cases of Alzheimer's disease were included in the meta-analysis. Six studies reported the association between ulcerative colitis and risk of Alzheimer's disease; five studies reported the association between Crohn's disease and risk of Alzheimer's disease. Meta-analysis combining these studies did not reveal any significant association of ulcerative colitis or Crohn's disease with risk of Alzheimer's disease. The pooled relative risks were 1.16 (95%CI: 0.96, 1.41) and 1.17 (95%CI: 0.84, 1.62) for ulcerative colitis and Crohn's disease, respectively. High heterogeneity was detected across the studies. Of note, there was an inverse association between inflammatory bowel disease related medication exposure and risk of Alzheimer's disease. The pooled relative risk of three studies for Alzheimer's disease was 0.86 (95%CI: 0.75, 0.99). No publication bias was detected.ConclusionThis study does not support the association of ulcerative colitis and Crohn's disease with the risk of Alzheimer's disease. However, medications for the treatment of inflammatory bowel disease might be associated with a lower risk of Alzheimer's disease.
| S-EPMC9878281 | biostudies-literature
Project description:Genetic correlations and an increased incidence of psychiatric disorders in inflammatory-bowel disease have been reported, but shared molecular mechanisms are unknown. We performed cross-tissue and multiple-gene conditioned transcriptome-wide association studies for 23 tissues of the gut-brain-axis using genome-wide association studies data sets (total 180,592 patients) for Crohn's disease, ulcerative colitis, primary sclerosing cholangitis, schizophrenia, bipolar disorder, major depressive disorder and attention-deficit/hyperactivity disorder. We identified NR5A2, SATB2, and PPP3CA (encoding a target for calcineurin inhibitors in refractory ulcerative colitis) as shared susceptibility genes with transcriptome-wide significance both for Crohn's disease, ulcerative colitis and schizophrenia, largely explaining fine-mapped association signals at nearby genome-wide association study susceptibility loci. Analysis of bulk and single-cell RNA-sequencing data showed that PPP3CA expression was strongest in neurons and in enteroendocrine and Paneth-like cells of the ileum, colon, and rectum, indicating a possible link to the gut-brain-axis. PPP3CA together with three further suggestive loci can be linked to calcineurin-related signaling pathways such as NFAT activation or Wnt.
| S-EPMC8776955 | biostudies-literature
Project description:BackgroundATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.ObjectivesTo perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.MethodsLiterature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model.ResultsOur analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003).ConclusionsATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.
| S-EPMC10859713 | biostudies-literature