Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study

AL-Eitan, Laith N.; Qudah, Malak Al; Qawasmeh, Majdi Al

doi:10.3390/biom10030356

Cited by 18 publications

(17 citation statements)

References 33 publications

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“…Thus, the plasmatic level was higher in rs3194051GG, rs987106AA and rs6897932CC genotypes, while the lowest was in the carriers of rs6897932TT. It is striking that the highest levels are detected in the genotype associated with severe and fatal cases, while the lowest levels are identified in the genotype TT, described previously as a protector for multiple sclerosis 11 , through of reduced exon splicing and production of soluble IL7R 23 , 24 .…”

Section: Discussionmentioning

confidence: 81%

“…These patients also predominated among the cases admitted to UCI, as well as rs987106TT genotype carriers. GG genotype has been associated with autoimmune pathologies like type I diabetes 21 and multiple sclerosis 11 , diseases that were not reported in the cases studied. Both SNPs are located in a potential regulatory zone whose effects have not been defined 14 and which it is different to those related to mutations observed in the combined severe immunodeficiency, disease that is not present in the adults studied.…”

Section: Discussionmentioning

confidence: 81%

“…Genetic variation in and the expression of the IL7R gene, as well as increased expression of receptor/ligand genes, contribute to the pathogenesis of autoimmune and chronic inflammatory diseases such as type 1 diabetes and multiple sclerosis 7 . Single-nucleotide polymorphism (SNP) of IL7R gene, such as rs6897932, rs3194051 and rs987106, has been associated with clinical severity in multiple sclerosis, hepatitis C and human immunodeficiency virus infection 11 – 14 . Four common haplotypes of the IL7R gene have been described in exonic and intronic zones and found to be associated with differential levels of sIL7R.…”

Section: Introductionmentioning

confidence: 99%

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IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study

Ampuero

Bahamonde

Tempio

et al. 2022

Sci Rep

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Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study

Ampuero

Bahamonde

Tempio

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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“…Despite LAG3/CD4 genes, SNVs have not been found to be associated with the risk for MS in GWAS, and taking into account the previously commented possible relationship between LAG3 protein and MS, it seems reasonable to investigate the possible association between LAG3/CD4 SNVs in the risk for MS. This issue has been of the topic of several studies, although the results have been controversial [ 20 , 21 , 22 , 23 ]. The current replication study aimed to establish whether the most common SNVs in these genes showed an association with the risk of MS in the Spanish Caucasian population.…”

Section: Introductionmentioning

confidence: 99%

Association between LAG3/CD4 Genes Variants and Risk for Multiple Sclerosis

García‐Martín

Agúndez

Gómez-Tabales

et al. 2022

IJMS

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Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population.

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“…Many of the cells in the innate and adaptive immune system respond to inflammation created within the central nervous system 4 . Mounting criteria have suggested that the major cause of MS is a combination of both environmental and genetic factors 5 – 7 . Genetic susceptibility plays an important role in the development of the disease, as more than 200 genetic variants associated with MS risk is identified through genome-wide association studies (GWAS) in the last few years 8 .…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Imani

Hojati

Khalilian

et al. 2021

Sci Rep

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Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

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Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study

Cited by 18 publications

References 33 publications

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study

Association between LAG3/CD4 Genes Variants and Risk for Multiple Sclerosis

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

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