The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women
IntroductionThe neutrophil cytosolic factor 1 (NCF1) rs201802880 polymorphism is a missense mutation resulting in an amino acid substitution from arginine to histidine at position 90, which impairs the function of NADPH oxidase. This casual variant confers an increased risk for multiple autoimmune d...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514296/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590802494160896 |
|---|---|
| author | Xinjun Hu Shasha Li Renliang Huang Ziwei Fu Chenyu Ma Zheng Cheng Hongjun Hu Qiaomiao Zhou Frank Petersen Xinhua Yu Xinhua Yu Junfeng Zheng |
| author_facet | Xinjun Hu Shasha Li Renliang Huang Ziwei Fu Chenyu Ma Zheng Cheng Hongjun Hu Qiaomiao Zhou Frank Petersen Xinhua Yu Xinhua Yu Junfeng Zheng |
| author_sort | Xinjun Hu |
| collection | DOAJ |
| description | IntroductionThe neutrophil cytosolic factor 1 (NCF1) rs201802880 polymorphism is a missense mutation resulting in an amino acid substitution from arginine to histidine at position 90, which impairs the function of NADPH oxidase. This casual variant confers an increased risk for multiple autoimmune disorders, including primary Sjögren’s syndrome and systemic lupus erythematosus. Given the high prevalence of this autoimmune disease risk variant in East Asia, we hypothesized that it may confer an evolutionary advantage by providing protection against infectious diseases.MethodsTo test this hypothesis, we investigated whether the NCF1 rs201802880 variant offers a protective effect against tuberculosis (TB), a historically significant and deadly infectious disease. Our study included 490 healthy controls and 492 TB patients who were genotyped for the NCF1 rs201802880 polymorphism.ResultsOur results showed that the NCF1 rs201802880 AA genotype was associated with a reduced risk of TB in women (OR= 0.25, 95% CI: 0.09-0.68, p=0.0023). Additionally, healthy individuals with the NCF1 rs201802880 AA genotype had significantly lower circulating white blood cell (5.56 ± 1.78 vs 6.43 ± 1.59, p=0.003) and neutrophil (3.23 ± 1.20 vs 3.74 ± 1.23, p = 0.02) counts compared to those with the GG or GA genotypes, with this difference being more pronounced in women than in men.ConclusionThis study demonstrates that the autoimmune disease-causal NCF1 variant is associated with a protective effect against TB infection. |
| format | Article |
| id | doaj-art-30f2a33cbd4544659947f8d910c95407 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-30f2a33cbd4544659947f8d910c954072025-01-23T06:56:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15142961514296The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in womenXinjun Hu0Shasha Li1Renliang Huang2Ziwei Fu3Chenyu Ma4Zheng Cheng5Hongjun Hu6Qiaomiao Zhou7Frank Petersen8Xinhua Yu9Xinhua Yu10Junfeng Zheng11Department of Infectious Diseases, The First Affiliated Hospital of Henan University of Science and Technology, Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, ChinaInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, ChinaDepartment of Genetics and Prenatal Diagnosis, Hainan Women and Children’s Medical Center, Haikou, Hainan, ChinaInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Henan University of Science and Technology, Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, ChinaInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, ChinaDepartment of Surgical Oncology, Xinxiang Central Hospital, The Fourth Clinical of Xinxiang Medical University, Xinxiang, ChinaDepartment of Genetics and Prenatal Diagnosis, Hainan Women and Children’s Medical Center, Haikou, Hainan, ChinaPriority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyDepartment of Genetics and Prenatal Diagnosis, Hainan Women and Children’s Medical Center, Haikou, Hainan, ChinaPriority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, ChinaIntroductionThe neutrophil cytosolic factor 1 (NCF1) rs201802880 polymorphism is a missense mutation resulting in an amino acid substitution from arginine to histidine at position 90, which impairs the function of NADPH oxidase. This casual variant confers an increased risk for multiple autoimmune disorders, including primary Sjögren’s syndrome and systemic lupus erythematosus. Given the high prevalence of this autoimmune disease risk variant in East Asia, we hypothesized that it may confer an evolutionary advantage by providing protection against infectious diseases.MethodsTo test this hypothesis, we investigated whether the NCF1 rs201802880 variant offers a protective effect against tuberculosis (TB), a historically significant and deadly infectious disease. Our study included 490 healthy controls and 492 TB patients who were genotyped for the NCF1 rs201802880 polymorphism.ResultsOur results showed that the NCF1 rs201802880 AA genotype was associated with a reduced risk of TB in women (OR= 0.25, 95% CI: 0.09-0.68, p=0.0023). Additionally, healthy individuals with the NCF1 rs201802880 AA genotype had significantly lower circulating white blood cell (5.56 ± 1.78 vs 6.43 ± 1.59, p=0.003) and neutrophil (3.23 ± 1.20 vs 3.74 ± 1.23, p = 0.02) counts compared to those with the GG or GA genotypes, with this difference being more pronounced in women than in men.ConclusionThis study demonstrates that the autoimmune disease-causal NCF1 variant is associated with a protective effect against TB infection.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514296/fullautoimmune diseases (AD)infectious diseasesneutrophil cytosolic factor 1 (NCF1)genetic associationevolutionary trade-offstuberculosis |
| spellingShingle | Xinjun Hu Shasha Li Renliang Huang Ziwei Fu Chenyu Ma Zheng Cheng Hongjun Hu Qiaomiao Zhou Frank Petersen Xinhua Yu Xinhua Yu Junfeng Zheng The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women Frontiers in Immunology autoimmune diseases (AD) infectious diseases neutrophil cytosolic factor 1 (NCF1) genetic association evolutionary trade-offs tuberculosis |
| title | The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women |
| title_full | The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women |
| title_fullStr | The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women |
| title_full_unstemmed | The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women |
| title_short | The autoimmune disease risk variant NCF1-His90 is associated with a reduced risk of tuberculosis in women |
| title_sort | autoimmune disease risk variant ncf1 his90 is associated with a reduced risk of tuberculosis in women |
| topic | autoimmune diseases (AD) infectious diseases neutrophil cytosolic factor 1 (NCF1) genetic association evolutionary trade-offs tuberculosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514296/full |
| work_keys_str_mv | AT xinjunhu theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT shashali theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT renlianghuang theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT ziweifu theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT chenyuma theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT zhengcheng theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT hongjunhu theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT qiaomiaozhou theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT frankpetersen theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT xinhuayu theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT xinhuayu theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT junfengzheng theautoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT xinjunhu autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT shashali autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT renlianghuang autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT ziweifu autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT chenyuma autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT zhengcheng autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT hongjunhu autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT qiaomiaozhou autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT frankpetersen autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT xinhuayu autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT xinhuayu autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen AT junfengzheng autoimmunediseaseriskvariantncf1his90isassociatedwithareducedriskoftuberculosisinwomen |