Mapping leprosy‐associated coding variants of interleukin genes by targeted sequencing

Df, Zhang; Li, Huilong; Zheng, Quanzhen; Bi, Rui; Xu, Min; Wang, Dong; Zhu, Guoping; Li, Yuye; Yao, Yong-Gang

doi:10.1111/cge.13945

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…We conditioned the gene-wise association of IL18R1 for the p.G423R and observed that the additional amino acid changes remained nominally significantly depleted in the gene ( P SKAT-O = 0.02) indicating that an increasing burden of nonsynonymous variants in IL18R1 is protective for leprosy independent of the p.G423R mutation. Rare amino acid changes in IL18R1 had also been identified in a case-control study of Chinese leprosy patients [ 25 , 26 ]. When we combined IL18R1 rare variants (MAF < 1%) detected in the Chinese and the Vietnamese population samples, significant depletion was maintained for rare variants in leprosy cases ( P CAST = 0.001) surpassing multiple test correction ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Age was not included as a covariate as the control group had more time to be exposed and develop leprosy and therefore age would not be a confounder in our analysis. To test the combined effect of IL18R1 rare protein-altering variants identified by our study with those described for the Chinese population [ 25 , 26 ], we used a Cohort Allelic Sums Test (CAST) implemented in AssotesteR [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

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Deep resequencing identifies candidate functional genes in leprosy GWAS loci

et al. 2021

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Leprosy is the second most prevalent mycobacterial disease globally. Despite the existence of an effective therapy, leprosy incidence has consistently remained above 200,000 cases per year since 2010. Numerous host genetic factors have been identified for leprosy that contribute to the persistently high case numbers. In the past decade, genetic epidemiology approaches, including genome-wide association studies (GWAS), identified more than 30 loci contributing to leprosy susceptibility. However, GWAS loci commonly encompass multiple genes, which poses a challenge to define causal candidates for each locus. To address this problem, we hypothesized that genes contributing to leprosy susceptibility differ in their frequencies of rare protein-altering variants between cases and controls. Using deep resequencing we assessed protein-coding variants for 34 genes located in GWAS or linkage loci in 555 Vietnamese leprosy cases and 500 healthy controls. We observed 234 nonsynonymous mutations in the targeted genes. A significant depletion of protein-altering variants was detected for the IL18R1 and BCL10 genes in leprosy cases. The IL18R1 gene is clustered with IL18RAP and IL1RL1 in the leprosy GWAS locus on chromosome 2q12.1. Moreover, in a recent GWAS we identified an HLA-independent signal of association with leprosy on chromosome 6p21. Here, we report amino acid changes in the CDSN and PSORS1C2 genes depleted in leprosy cases, indicating them as candidate genes in the chromosome 6p21 locus. Our results show that deep resequencing can identify leprosy candidate susceptibility genes that had been missed by classic linkage and association approaches.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Deep resequencing identifies candidate functional genes in leprosy GWAS loci

et al. 2021

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“…Another study in India showed that the locus on chromosome 10p13 is associated with an increased risk of PB-type leprosy. (35) The risk factor for leprosy from genetic factors can occur eight times with a range of 5.9-10.6 times. 36 Further research needs to be conducted to assess the correlation of serum TGF-β levels and IgM anti-PGL-1 levels not only in household contacts of multibacillary leprosy patients but to compare various types of leprosy in endemic areas and healthy people using the case-control method, and prognostic observations can be carried out with the cohort method with a larger sample.…”

Section: Auc: 775%mentioning

confidence: 99%

Levels of TGF- Serum Positively Correlated with Levels of IgM Anti PGL-1 In Household Contacts of Multibacillary Leprosy Patients

Primasari,

Rusyati,

Karmila

et al. 2023

J Biomedika dan Kesehat

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Background Leprosy is a chronic progressive infectious disease. Phenolic glycolipid-1 (PGL-1) is an antigen of Mycobacterium leprae, which can trigger the host’s antibody response. Transforming growth factorβ (TGF-β) plays an immunosuppressive role when the host is exposed to PGL-1 antigen or other M. leprae antigens. This study aims to determine the correlation of TGF-β levels with IgM anti-PGL-1 levels in patients with multibacillary leprosy household contacts. Methods Observational analytical study with a cross-sectional approach. The study subjects consisted of 48 household contact subjects and 24 non-household contact subjects aged 15-65 years old who were selected by consecutive sampling based on inclusion and exclusion criteria. 3 mL of venous blood samples were taken and then examined for IgM anti-PGL-1 and TGF-β with the ELISA kit. Data analysis was carried out using SPSS version 23, and a p-value <0.05 was significant. Results The mean level of IgM anti-PGL-1 in the household contact group was 685.46 ± 290.79 u/mL, while in the non-household contact group was 345.50 ± 206.58 u/mL. The mean TGF-β level in household contact groups was 256.69 ± 127.41 pg/mL, while in the non-household contact group was 144.85 ± 36.73 pg/mL (p<0.001). This study found a moderate positive relationship (r=0.450, p<0.001) between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group. Conclusions The mean level of IgM anti-PGL-1 and TGF-β in household contacts is higher than in non-household contacts, with a significant difference. There is a moderate positive significant relationship between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group.

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“…The role of IL-6 as an anti-inflammatory myokine is mediated through its inhibitory effect on Tumor Necrosis Factor (TNF)-alpha and IL-1, as well as the activation of IL-1 and IL-10. 3 Interleukin 6 can be used as a potential marker to identify the risk of household contacts becoming clinical leprosy. This risk is higher in low nutritional status (underweight, anemia, and iron deficiency).…”

Section: Introductionmentioning

confidence: 99%

Positive Correlation of Plasma Interleukin-6 Levels with Immunoglobulin M (IgM) Anti Phenolic Glycolipid-1 (PGL-1) Levels in Household Contacts of Multibacillary Leprosy Patients

2023

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Background/aim: Leprosy is a chronic infectious disease that can be cured but causes high morbidity because it causes disability. Leprosy is caused by the bacterium Mycobacterium leprae, an obligate intracellular virulence factor in the form of phenolic glycolipid-1 (PGL-1), a capsule component in M. leprae. This study aims for known Increased IL-6 correlation with IgM anti PGL-1 level in household contacts of multibacillary leprosy patient. Methods: Analytical observational study with a cross-sectional approach. The sample consisted of 42 household contact persons and 22 non-contact samples aged 18-65 years who were selected through consecutive sampling according to the inclusion and exclusion criteria. Samples of 3 millilitres of venous blood were taken, which would then be examined for PGL-1 and IL-6 with the ELISA kit. Data analysis with SPSS version 23 and p-value <0.05 was significant Results: The average anti-PGL-1 IgM level in the household contact group was 636.76±288.45 u/ml, while in the non-contact group, it was 211.00±237.43 u/ml. The average IL-6 level in the household contact group was 20.28 ± 12.54 pg/ml, while in the non-contact group, it was 8.29 ± 2.88 pg/ml. There was a significant difference in the levels of IL-6 and anti-PGL-1 IgM in the household contact and non-contact groups (p<0.001). This study found a strong positive relationship (r=0.620, p<0.001) between IL-6 levels and anti-PGL-1 IgM levels. Conclusion: IgM anti-PGL-1 and IL-6 levels in household contacts were higher than in non-contacts, with a significant difference. There is a significant positive relationship between IL-6 and anti-PGL-1 IgM levels. Keywords: leprosy, contacts, IgM anti-PGL-1, IL-6

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Mapping leprosy‐associated coding variants of interleukin genes by targeted sequencing

Cited by 4 publications

References 38 publications

Deep resequencing identifies candidate functional genes in leprosy GWAS loci

Deep resequencing identifies candidate functional genes in leprosy GWAS loci

Levels of TGF- Serum Positively Correlated with Levels of IgM Anti PGL-1 In Household Contacts of Multibacillary Leprosy Patients

Positive Correlation of Plasma Interleukin-6 Levels with Immunoglobulin M (IgM) Anti Phenolic Glycolipid-1 (PGL-1) Levels in Household Contacts of Multibacillary Leprosy Patients

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