Multiple sclerosis is accompanied by lack of KIR2DS1 gene: A meta-analysis

Shahsavar, Farhad; Mapar, Shaghayegh; Ahmadi, Seyyed Amir Yasin

doi:10.1016/j.gdata.2016.09.009

Cited by 13 publications

(10 citation statements)

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“…Other than the justification above, another justification is that the ligands of activating KIRs are not necessarily HLAs; rather, they are still unknown [36], [53]. This, can be pointed out as the limitation of the previous studies.…”

Section: Resultsmentioning

confidence: 99%

“…Killer cell immunoglobulin-like receptors (KIRs) (also called as CD158) are polymorphic glycoproteins expressed on cell surface of NKs and T cell subsets [35]. KIR gene family is highly polymorphic and its genomic diversity is achieved through differences in gene content as well as allelic polymorphism [36], [37]. Of course the most polymorphic loci in human genome is HLA [38] which the molecules of its, are in direct contact with KIR molecules.…”

Section: Introductionmentioning

confidence: 99%

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Colorectal cancer and the KIR genes in the human genome: A meta-analysis

et al. 2016

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Colorectal cancer is one of the most common types of inflammation-based cancers and is occurred due to growth and spread of cancer cells in colon and/or rectum. Previously genetic association of cell cycle genes, both proto-oncogenes and the tumor suppressors has been proved. But there were few studies about association of immune related genes such as killer-cell immunoglobulin-like receptors (KIRs). Thus we intend to perform a meta-analysis to find the association of different genes of KIR and susceptibility to be affected by colorectal cancer. The overall population of the four studies investigated in our meta-analysis was 953 individuals (470 individuals with colorectal cancer and 483 individuals in control groups). After the analyses, we concluded that colorectal cancer is affected by KIR2DS5 and also there were no protecting gene. This result shows the inflammatory basis of this cancer. In other words, in contrast to leukemia and blood cancers, colorectal cancers seem to be affected by hyper activity of natural killer-cells (NKs). Whys and therefore of this paradox, is suggested to be investigated further.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Colorectal cancer and the KIR genes in the human genome: A meta-analysis

et al. 2016

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“…In the Sardinian population, MS has been found associated with the HLA-A*30, -B*18, -C*05, -DR*03 extended haplotype and the HLA-DR*03 and HLA-DQ*02 alleles [30, 31]. While many authors link MS to the HLA system, only a minority of studies have reported association between MS and KIR genes and the results are either contradictory or remain unconfirmed [32–34]. All these studies applied standard statistical tests which are useful in detecting single alleles and/or haplotypes that either confer protection or susceptibility to disease.…”

Section: Discussionmentioning

confidence: 99%

Entropy of human leukocyte antigen and killer-cell immunoglobulin-like receptor systems in immune-mediated disorders: A pilot study on multiple sclerosis

et al. 2019

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BackgroundEntropy is a thermodynamic variable statistically correlated with the disorder of a system. The hypothesis that entropy can be used to identify potentially unhealthy conditions was first suggested by Schrödinger, one of the founding fathers of quantum mechanics. Shannon later defined entropy as the quantity of information stored in a system. Shannon’s entropy has the advantage of being adaptable across a variety of disciplines, including genetic studies on complex immunogenetic systems such as the human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) systems.MethodsIn our study, entropy associated to the HLA and KIR systems was compared between a cohort of 619 Sardinian healthy controls and a group of 270 patients affected by multiple sclerosis (MS), the latter stratified into 81 patients with primary progressive multiple sclerosis (PPMS) and 189 patients with relapsing remitting multiple sclerosis (RRMS).ResultsThe entropy associated to HLA four-loci haplotypes (A, B, C, DR) and combinations of two inhibitory KIR genes was significantly higher in patients affected by RRMS than in healthy controls. No significant differences were observed for patients with PPMS. By calculating the total HLA and KIR entropy ratio in each subject, it was possible to determine the individual risk of developing MS, particularly RRMS.ConclusionsIn addition to the standard statistical methods used to evaluate immunogenetic parameters associated to immune-mediated disease, the analysis of entropy measures the global disorder status deriving from these parameters. This innovative approach may represent a useful complementary tool to the risk assessment of immune-mediated disorders. Improved risk assessment is particularly important for family members of patients with MS. However, further investigation is warranted to confirm our findings and to evaluate the validity of the entropy-based method in other types of immune-mediated disorders.

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“…To our knowledge, this is the first meta-analysis that examines KIR effects on HIV acquisition. By extension, associations of the KIR polymorphisms have been reported in a number of meta-analyses that included disease endpoints such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus and multiple sclerosis [54–57]. The only other meta-analysis for KIR polymorphisms with another infectious disease is that of Gauthiez et al’s examination of the Hepatitis C Virus (HCV) infection with HCV clearance [58].…”

Section: Discussionmentioning

confidence: 99%

Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis

Chaisri¹,

Pabalan²,

Tabunhan³

et al. 2019

PLoS ONE

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BackgroundGenetic involvement of Killer Immunoglobulin-like Receptor (KIR) polymorphisms and Human Immunodeficiency Virus (HIV)-exposed seronegative (HESN) compared to HIV-infected (HIVI) individuals has been reported. However, inconsistency of the outcomes reduces precision of the estimates. A meta-analysis was applied to obtain more precise estimates of association.MethodsA multi-database literature search yielded thirteen case-control studies. Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P-value of ≤ 0.05. We used two levels of analyses: (1) gene content that included 13 KIR polymorphisms (2DL1-3, 2DL5A, 2DL5B, 2DS1-3, 2DS4F, 2DS4D, 2DS5, 3DL1 and 3DS1); and (2) 3DL1/S1 genotypes. Subgroup analysis was ethnicity-based (Caucasians, Asians and Africans). Outlier treatment was applied to heterogeneous effects which dichotomized the outcomes into pre-outlier (PRO) and post-outlier (PSO). Multiple comparisons were addressed with the Bonferroni correction.ResultsWe generated 52 and 18 comparisons from gene content and genotype analyses, respectively. Of the 70 comparisons, 13 yielded significant outcomes, two (indicating reduced risk) of which survived the Bonferroni correction (Pc). These protective effects pointed to the Caucasian subgroup in 2DL3 (OR 0.19, 95% CI 0.09, 0.40, Pc < 10−3) and 3DS1S1 (OR 0.37, 95% CI 0.24, 0.56, Pc < 10−3). These two PSO outcomes yielded effects of increased magnitude and precision, as well as raised significance and deemed robust by sensitivity analysis. Of the two, the 2DL3 effect was improved with a test of interaction (Pc interaction < 10−4).ConclusionMultiple meta-analytical treatments presented strong evidence of the protective effect (up to 81%) of the KIR polymorphisms (2DL3 and 3DS1S1) among Caucasians. The Asian and African outcomes were inconclusive due to the low number of studies.

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Multiple sclerosis is accompanied by lack of KIR2DS1 gene: A meta-analysis

Cited by 13 publications

References 40 publications

Colorectal cancer and the KIR genes in the human genome: A meta-analysis

Colorectal cancer and the KIR genes in the human genome: A meta-analysis

Entropy of human leukocyte antigen and killer-cell immunoglobulin-like receptor systems in immune-mediated disorders: A pilot study on multiple sclerosis

Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis

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