Correlation between the polymorphisms of inhibition genes <i>WIF1</i> and <i>DKK1</i> in WNT signaling pathway and the susceptibility to tuberculosis in Chinese Han population _West China Medical Journal

Authors：

LIU Tangyuheng , WANG Nian , SONG Jiajia , HU Xuejiao , ZHAO Zhenzhen , PENG Wu , BAI Hao , WU Qian ,  YING Binwu

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

YING Binwu, Email: binwuying@126.com

Keywords：

Tuberculosis; WNT signaling pathway; WIF1 gene; DKK1 gene; Single nucleotide polymorphism

DOI：

10.7507/1002-0179.201807066

Video：

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Objective To explore the relationships between the polymorphisms of inhibitor genes WIF1 and DKK1 in WNT signaling pathway and susceptibility to tuberculosis, clinical characteristics and laboratory indexes. Methods From December 2014 to November 2016, 475 tuberculosis patients and 370 healthy controls of West China Hospital of Sichuan University were enrolled in the study, and the clinical data of the subjects were collected. High-throughput genotyping technique was used to detect the polymorphisms of WIF1 rs58635985 and DKK1 rs11001548 in WNT signaling pathway. The allele frequency distribution, genotype, genetic model, clinical features and laboratory indexes of two single nucleotide polymorphisms were analyzed by χ² test and logistic regression analysis. Results There was no significant difference in the allele frequency distribution (P=0.275, 0.949), genotype (P=0.214, 0.659) or genetic models: additive model (P=0.214, 0.659), dominant model (P=0.414, 0.827), recessive model (P=0.227, 0.658) of rs58635985 and rs11001548 between the tuberculosis group and the healthy control group. Subgroup analysis showed no significant difference in allele and genotype distribution between rs58635985 and rs11001548 (pulmonary tuberculosis group vs. healthy control group: P>0.05; pulmonary tuberculosis groupvs. extra-pulmonary tuberculosis group: P>0.05). There was no significant difference in the clinical features (fever, night sweat, fatigue,etc.) or laboratory indexes (complete blood count, erythrocyte sedimentation rate, TB-DNA, etc.) (P>0.05). Conclusions There is no association between rs58635985 of WIF1 gene or rs11001548 of DKK1 gene and genetic susceptibility, clinical characteristics and laboratory indexes in Han population in Western China. To expand the sample size for verification and analysis in different populations is necessary.

Citation： LIU Tangyuheng, WANG Nian, SONG Jiajia, HU Xuejiao, ZHAO Zhenzhen, PENG Wu, BAI Hao, WU Qian, YING Binwu. Correlation between the polymorphisms of inhibition genes WIF1 and DKK1 in WNT signaling pathway and the susceptibility to tuberculosis in Chinese Han population . West China Medical Journal, 2018, 33(8): 958-965. doi: 10.7507/1002-0179.201807066 Copy

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2.	Cobat A, Barrera LF, Henao H, et al. Tuberculin skin test reactivity is dependent on host genetic background in Colombian tuberculosis household contacts. Clin Infect Dis, 2012, 54(7): 968-971.
3.	Ma MJ, Xie LP, Wu SC, et al. Toll-like receptors, tumor necrosis factor-α, and interleukin-10 gene polymorphisms in risk of pulmonary tuberculosis and disease severity. Hum Immunol, 2010, 71(10): 1005-1010.
4.	Villaseñor T, Madrid-Paulino E, Maldonado-Bravo R, et al. Activation of the Wnt pathway by Mycobacterium tuberculosis: a Wnt-Wnt situation. Front Immunol, 2017, 8(50): 50.
5.	Zhang B, Ma JX. Wnt pathway antagonists and angiogenesis. Protein Cell, 2010, 1(10): 898-906.
6.	Hu X, Zhou J, Chen X, et al. Pathway analyses identify novel variants in the WNT signaling pathway associated with tuberculosis in Chinese population. Sci Rep, 2016, 6: 28530.
7.	周汶静, 胡雪姣, 张晶雅, 等. Wnt 信号通路基因单核苷酸多态性与中国西部藏族人群结核易感性研究. 四川大学学报: 医学版, 2016, 47(6): 920-925.
8.	Frieden TR, Sterling TR, Munsiff SS, et al. Tuberculosis. Lancet, 2003, 362(9387): 887-899.
9.	Sveinbjornsson G, Gudbjartsson DF, Halldorsson BV, et al. HLA class Ⅱ sequence variants influence tuberculosis risk in populations of European ancestry. Nat Genet, 2016, 48(3): 318-322.
10.	Fan L, Xiao H, Mai G, et al. Impaired M. tuberculosis antigen-specific IFN-γ response without IL-17 enhancement in patients with severe cavitary pulmonary tuberculosis. PLoS One, 2015, 10(5): e0127087.
11.	石娟, 杨佳丽, 马凌洁, 等. 经典 Wnt 信号途径在肺脏上皮细胞抗结核分枝杆菌感染中的作用. 中国生物工程杂志, 2013, 33(12): 9-14.
12.	Lambiv WL, Vassallo I, Delorenzi M, et al. The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence. Neuro Oncol, 2011, 13(7): 736-747.
13.	Zhang J, Zhang X, Zhao X, et al. DKK1 promotes migration and invasion of non-small cell lung cancer via β-catenin signaling pathway. Tumour Biol, 2017, 39(7): 1010428317703820.
14.	Hu J, Dong A, Fernandez-Ruiz V, et al. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res, 2009, 69(17): 6951-6959.
15.	Ko YB, Kim BR, Yoon K, et al. WIF1 can effectively co-regulate pro-apoptotic activity through the combination with DKK1. Cell Signal, 2014, 26(11): 2562-2572.
16.	Wang SH, Xu F, Dang HX, et al. Genetic variations in the Wnt signaling pathway affect lung function in asthma patients. Genet Mol Res, 2013, 12(2): 1829-1833.
17.	Feng ZY, Xu XH, Cen DZ, et al. miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1. Eur Rev Med Pharmacol Sci, 2017, 21(21): 4844-4852.
18.	Liu S, Tian W, Wang J, et al. Two single-nucleotide polymorphisms in the DKK1 gene are associated with developmental dysplasia of the hip in the Chinese Han female population. Genet Test Mol Biomarkers, 2014, 18(8): 557-561.
19.	Jones MR, Chua A, Chen YD, et al. Harnessing expression data to identify novel candidate genes in polycystic ovary syndrome. PLoS One, 2011, 6(5): e20120.
20.	Wu J, Zhang J, Zhen Z, et al. Genetic variations of DICKKOPF family genes might not be associated with gastric cancer susceptibility. BMC Gastroenterol, 2016, 16(1): 78.

1. World Health Organization. Global tuberculosis report 2016: WHO/HTM/TB/2016.13. Geneva: World Health Organization, 2016. http://apps.who.int/medicinedocs/documents/s23098en/ s23098en.pdf.
2. Cobat A, Barrera LF, Henao H, et al. Tuberculin skin test reactivity is dependent on host genetic background in Colombian tuberculosis household contacts. Clin Infect Dis, 2012, 54(7): 968-971.
3. Ma MJ, Xie LP, Wu SC, et al. Toll-like receptors, tumor necrosis factor-α, and interleukin-10 gene polymorphisms in risk of pulmonary tuberculosis and disease severity. Hum Immunol, 2010, 71(10): 1005-1010.
4. Villaseñor T, Madrid-Paulino E, Maldonado-Bravo R, et al. Activation of the Wnt pathway by Mycobacterium tuberculosis: a Wnt-Wnt situation. Front Immunol, 2017, 8(50): 50.
5. Zhang B, Ma JX. Wnt pathway antagonists and angiogenesis. Protein Cell, 2010, 1(10): 898-906.
6. Hu X, Zhou J, Chen X, et al. Pathway analyses identify novel variants in the WNT signaling pathway associated with tuberculosis in Chinese population. Sci Rep, 2016, 6: 28530.
7. 周汶静, 胡雪姣, 张晶雅, 等. Wnt 信号通路基因单核苷酸多态性与中国西部藏族人群结核易感性研究. 四川大学学报: 医学版, 2016, 47(6): 920-925.
8. Frieden TR, Sterling TR, Munsiff SS, et al. Tuberculosis. Lancet, 2003, 362(9387): 887-899.
9. Sveinbjornsson G, Gudbjartsson DF, Halldorsson BV, et al. HLA class Ⅱ sequence variants influence tuberculosis risk in populations of European ancestry. Nat Genet, 2016, 48(3): 318-322.
10. Fan L, Xiao H, Mai G, et al. Impaired M. tuberculosis antigen-specific IFN-γ response without IL-17 enhancement in patients with severe cavitary pulmonary tuberculosis. PLoS One, 2015, 10(5): e0127087.
11. 石娟, 杨佳丽, 马凌洁, 等. 经典 Wnt 信号途径在肺脏上皮细胞抗结核分枝杆菌感染中的作用. 中国生物工程杂志, 2013, 33(12): 9-14.
12. Lambiv WL, Vassallo I, Delorenzi M, et al. The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence. Neuro Oncol, 2011, 13(7): 736-747.
13. Zhang J, Zhang X, Zhao X, et al. DKK1 promotes migration and invasion of non-small cell lung cancer via β-catenin signaling pathway. Tumour Biol, 2017, 39(7): 1010428317703820.
14. Hu J, Dong A, Fernandez-Ruiz V, et al. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res, 2009, 69(17): 6951-6959.
15. Ko YB, Kim BR, Yoon K, et al. WIF1 can effectively co-regulate pro-apoptotic activity through the combination with DKK1. Cell Signal, 2014, 26(11): 2562-2572.
16. Wang SH, Xu F, Dang HX, et al. Genetic variations in the Wnt signaling pathway affect lung function in asthma patients. Genet Mol Res, 2013, 12(2): 1829-1833.
17. Feng ZY, Xu XH, Cen DZ, et al. miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1. Eur Rev Med Pharmacol Sci, 2017, 21(21): 4844-4852.
18. Liu S, Tian W, Wang J, et al. Two single-nucleotide polymorphisms in the DKK1 gene are associated with developmental dysplasia of the hip in the Chinese Han female population. Genet Test Mol Biomarkers, 2014, 18(8): 557-561.
19. Jones MR, Chua A, Chen YD, et al. Harnessing expression data to identify novel candidate genes in polycystic ovary syndrome. PLoS One, 2011, 6(5): e20120.
20. Wu J, Zhang J, Zhen Z, et al. Genetic variations of DICKKOPF family genes might not be associated with gastric cancer susceptibility. BMC Gastroenterol, 2016, 16(1): 78.

West China Medical Journal

Correlation between the polymorphisms of inhibition genes WIF1 and DKK1 in WNT signaling pathway and the susceptibility to tuberculosis in Chinese Han population

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