Associations of genetic polymorphisms in <i>STAT6</i> with tuberculosis susceptibility in western Chinese Han population_West China Medical Journal

Authors：

LÜ Yanghua ^1,2 , ZHAO Zhenzhen ¹ , ZHOU Wenjing ¹ , SONG Xingbo ¹ , LI Jing ^1,2 ,  YING Binwu ¹

1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Laboratory Medicine, Panzhihua Central Hospital, Panzhihua, Sichuan 617067, P. R. China;

Corresponding author：

YING Binwu, Email: docbwy@126.com

Keywords：

Tuberculosis; Signal transducers and activators of transcription 6; Susceptibility; Single nucleotide polymorphism

DOI：

10.7507/1002-0179.201907073

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Objective To investigate the associations of signal transducers and activators of transcription 6 (STAT6) gene polymorphisms with susceptibility to tuberculosis in western Chinese Han population.Methods A total of 900 tuberculosis patients and 1 534 healthy controls of West China Hospital of Sichuan University were enrolled from January 2014 to February 2016. Improved multiplex ligation detection reaction method was used to detect four polymorphisms (rs1059513, rs73118432, rs841718, and rs10783813) of STAT6 gene. The allelic frequencies, genetic types, and different genetic models were analyzed using the chi-square test and unconditional logistic regression models to evaluate the associations of STAT6 gene with tuberculosis risk.Results Eventually, a total of 856 cases and 1 511 health controls were recruited in our study. No significant differences were observed in allele frequencies, genotype distributions, or genetic models (additive model, dominant model and recessive model) at rs1059513, rs73118432, rs841718, and rs10783813 in STAT6 gene (P>0.05). We found a strong linkage disequilibrium among rs73118432, rs841718, and rs10783813, but there was no statistical difference in haplotype frequencies between the two groups (P>0.05).Conclusions STAT6 gene rs73118432, rs841718, rs10783813, and rs1059513 polymorphisms might have no associations with tuberculosis susceptibility in western Chinese Han population. Further studies with larger sample sizes are needed to comfirm these results.

Citation： LÜ Yanghua, ZHAO Zhenzhen, ZHOU Wenjing, SONG Xingbo, LI Jing, YING Binwu. Associations of genetic polymorphisms in STAT6 with tuberculosis susceptibility in western Chinese Han population. West China Medical Journal, 2019, 34(8): 857-862. doi: 10.7507/1002-0179.201907073 Copy

1.	Walker TM, Kohl TA, Omar SV, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis, 2015, 15(10): 1193-1202.
2.	Möller M, Hoal EG. Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis, 2010, 90(2): 71-83.
3.	van der Eijk EA, van de Vosse E, Vandenbroucke JP, et al. Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited. Am J Respir Crit Care Med, 2007, 176(12): 1281-1288.
4.	Van Tong H, Velavan TP, Thye T, et al. Human genetic factors in tuberculosis: an update. Trop Med Int Health, 2017, 22(9): 1063-1071.
5.	Shea-Donohue T, Qin B, Smith A. Parasites, nutrition, immune responses and biology of metabolic tissues. Parasite Immunol, 2017, 39(5).
6.	Kisuya J, Chemtai A, Raballah E, et al. The role of antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus. Pan Afr Med J, 2018, 31: 166.
7.	Ozeki Y, Hirayama Y, Takii T, et al. Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guérin. Vaccine, 2011, 29(40): 6881-6887.
8.	中华人民共和国卫生部. 结核病分类标准: WS 196－2017. 北京: 人民卫生出版社, 2017.
9.	Hijikata M, Shojima J, Matsushita I, et al. Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese. Hum Genet, 2012, 131(5): 675-682.
10.	Takeda K, Tanaka T, Shi W, et al. Essential role of Stat6 in IL-4 signalling. Nature, 1996, 380(6575): 627-630.
11.	Nelms K, Keegan AD, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol, 1999, 17: 701-738.
12.	Chinen T, Kobayashi T, Ogata H, et al. Suppressor of cytokine signaling-1 regulates inflammatory bowel disease in which both IFN-γ and IL-4 are involved. Gastroenterology, 2006, 130(2): 373-388.
13.	Harris J, De Haro SA, Master SS, et al. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity, 2007, 27(3): 505-517.
14.	Wurster AL, Rodgers VL, White MF, et al. Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL. J Biol Chem, 2002, 277(30): 27169-27175.
15.	Mayr C. Evolution and biological roles of alternative 3’UTRs. Trends Cell Biol, 2016, 26(3): 227-237.
16.	Moffatt MF, Gut IG, Demenais F, et al. A large-scale, consortium based genomewide association study of asthma. N Engl J Med, 2010, 363(13): 1211-1221.
17.	Paternoster L, Standl M, Chen CM, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet, 2011, 44(2): 187-192.
18.	van Ginkel CD, Pettersson ME, Dubois AEJ, et al. Association of stat6 gene variants with food allergy diagnosed by double-blind placebo-controlled food challenges. Allergy, 2018, 73(6): 1337-1341.
19.	Yabiku K, Hayashi M, Komiya I, et al. Polymorphisms of interleukin (IL)-4 receptor alpha and signal transducer and activator of transcription-6 (Stat6) are associated with increased IL-4R alpha-Stat6 signalling in lymphocytes and elevated serum IgE in patients with Graves’ disease. Clin Exp Immunol, 2007, 148(3): 425-431.
20.	Kawashige S, Kanazawa T, Tsutsumi A, et al. An association study of the signal transducer and activator of transcription 6 gene with periodic psychosis. Psychiatry Investig, 2008, 5(1): 41-44.
21.	范广来, 魏红, 武荣, 等. STAT4和STAT6在子痫前期胎盘及血清组织中的表达及意义. 中国妇幼保健, 2016, 31(6): 1264-1267.
22.	Godava M, Kopriva F, Bohmova J, et al. Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2012, 156(3): 236-247.

1. Walker TM, Kohl TA, Omar SV, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis, 2015, 15(10): 1193-1202.
2. Möller M, Hoal EG. Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis, 2010, 90(2): 71-83.
3. van der Eijk EA, van de Vosse E, Vandenbroucke JP, et al. Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited. Am J Respir Crit Care Med, 2007, 176(12): 1281-1288.
4. Van Tong H, Velavan TP, Thye T, et al. Human genetic factors in tuberculosis: an update. Trop Med Int Health, 2017, 22(9): 1063-1071.
5. Shea-Donohue T, Qin B, Smith A. Parasites, nutrition, immune responses and biology of metabolic tissues. Parasite Immunol, 2017, 39(5).
6. Kisuya J, Chemtai A, Raballah E, et al. The role of antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus. Pan Afr Med J, 2018, 31: 166.
7. Ozeki Y, Hirayama Y, Takii T, et al. Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guérin. Vaccine, 2011, 29(40): 6881-6887.
8. 中华人民共和国卫生部. 结核病分类标准: WS 196－2017. 北京: 人民卫生出版社, 2017.
9. Hijikata M, Shojima J, Matsushita I, et al. Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese. Hum Genet, 2012, 131(5): 675-682.
10. Takeda K, Tanaka T, Shi W, et al. Essential role of Stat6 in IL-4 signalling. Nature, 1996, 380(6575): 627-630.
11. Nelms K, Keegan AD, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol, 1999, 17: 701-738.
12. Chinen T, Kobayashi T, Ogata H, et al. Suppressor of cytokine signaling-1 regulates inflammatory bowel disease in which both IFN-γ and IL-4 are involved. Gastroenterology, 2006, 130(2): 373-388.
13. Harris J, De Haro SA, Master SS, et al. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity, 2007, 27(3): 505-517.
14. Wurster AL, Rodgers VL, White MF, et al. Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL. J Biol Chem, 2002, 277(30): 27169-27175.
15. Mayr C. Evolution and biological roles of alternative 3’UTRs. Trends Cell Biol, 2016, 26(3): 227-237.
16. Moffatt MF, Gut IG, Demenais F, et al. A large-scale, consortium based genomewide association study of asthma. N Engl J Med, 2010, 363(13): 1211-1221.
17. Paternoster L, Standl M, Chen CM, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet, 2011, 44(2): 187-192.
18. van Ginkel CD, Pettersson ME, Dubois AEJ, et al. Association of stat6 gene variants with food allergy diagnosed by double-blind placebo-controlled food challenges. Allergy, 2018, 73(6): 1337-1341.
19. Yabiku K, Hayashi M, Komiya I, et al. Polymorphisms of interleukin (IL)-4 receptor alpha and signal transducer and activator of transcription-6 (Stat6) are associated with increased IL-4R alpha-Stat6 signalling in lymphocytes and elevated serum IgE in patients with Graves’ disease. Clin Exp Immunol, 2007, 148(3): 425-431.
20. Kawashige S, Kanazawa T, Tsutsumi A, et al. An association study of the signal transducer and activator of transcription 6 gene with periodic psychosis. Psychiatry Investig, 2008, 5(1): 41-44.
21. 范广来, 魏红, 武荣, 等. STAT4和STAT6在子痫前期胎盘及血清组织中的表达及意义. 中国妇幼保健, 2016, 31(6): 1264-1267.
22. Godava M, Kopriva F, Bohmova J, et al. Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2012, 156(3): 236-247.

West China Medical Journal

Associations of genetic polymorphisms in STAT6 with tuberculosis susceptibility in western Chinese Han population

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