Li Liang1, Huijuan Liu2, Jun Yue1, Li-Rong Liu1, Min Han1, Liu-Lin Luo1, Yan-Lin Zhao3, Heping Xiao1. 1. 1 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai, China . 2. 2 Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin, China . 3. 3 National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing, China .
Abstract
BACKGROUND: Hepcidin is a 25-amino acid peptide produced by the liver in response to inflammation and iron overload. It is encoded by the hepcidin antimicrobial peptide (HAMP) gene and plays a key role in innate immunity. Previous studies have reported that a -582 A>G polymorphism in the HAMP promoter (HAMP-P) affects hepcidin expression, causing susceptibility to various bacterial and viral pathogens. However, it is not known whether the HAMP-P -582 A>G polymorphism is associated with tuberculosis (TB) susceptibility. AIMS: The objective of the current study was to examine the relationship between the HAMP-P -582 A>G polymorphism and TB susceptibility in a Chinese Han population. METHODS: Han Chinese subjects examined included 500 pulmonary TB, 386 extrapulmonary TB, and 600 healthy control subjects. We analyzed correlations between the hepcidin promoter -582 A>G polymorphism and disease susceptibility and then examined the regulatory effects of the -582 A>G variant on hepcidin production in CD14+ monocyte cultures stimulated with lipoarabinomannan derived from Mycobacterium tuberculosis. RESULTS: Our findings indicate that the HAMP-P -582 A>G polymorphism (rs10421768) is associated with susceptibility to extrapulmonary TB, but not pulmonary TB. CD14+ monocytes from individuals with the rs10421768 GG genotype secreted significantly less hepcidin in response to M. tuberculosis lipoarabinomannan compared with cells from individuals with either the AA or AG genotypes. CONCLUSIONS: The G allele of the HAMP-P -582 A>G gene may play a critical role in TB susceptibility.
BACKGROUND: Hepcidin is a 25-amino acid peptide produced by the liver in response to inflammation and iron overload. It is encoded by the hepcidin antimicrobial peptide (HAMP) gene and plays a key role in innate immunity. Previous studies have reported that a -582 A>G polymorphism in the HAMP promoter (HAMP-P) affects hepcidin expression, causing susceptibility to various bacterial and viral pathogens. However, it is not known whether the HAMP-P -582 A>G polymorphism is associated with tuberculosis (TB) susceptibility. AIMS: The objective of the current study was to examine the relationship between the HAMP-P -582 A>G polymorphism and TB susceptibility in a Chinese Han population. METHODS: Han Chinese subjects examined included 500 pulmonary TB, 386 extrapulmonary TB, and 600 healthy control subjects. We analyzed correlations between the hepcidin promoter -582 A>G polymorphism and disease susceptibility and then examined the regulatory effects of the -582 A>G variant on hepcidin production in CD14+ monocyte cultures stimulated with lipoarabinomannan derived from Mycobacterium tuberculosis. RESULTS: Our findings indicate that the HAMP-P -582 A>G polymorphism (rs10421768) is associated with susceptibility to extrapulmonary TB, but not pulmonary TB. CD14+ monocytes from individuals with the rs10421768 GG genotype secreted significantly less hepcidin in response to M. tuberculosis lipoarabinomannan compared with cells from individuals with either the AA or AG genotypes. CONCLUSIONS: The G allele of the HAMP-P -582 A>G gene may play a critical role in TB susceptibility.
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