Original Article

Polymorphisms of Fatty Acid Elongase 2 Gene Afftects Risk of Pulmonary Tuberculosis in China Han Population



Background: As an infectious disease closely related to Mycobacterium tuberculosis, autoimmunity, inflammation, environment and heredity, the relationship between the single nucleotide polymorphism of elongase 2 gene and the susceptibility to tuberculosis is still unknown.

Methods: Between January 2016 and November 2018, a hospital-based case-control study was conducted. This epidemiological survey was conducted in both hospitals every three months. rs3798719, rs1570069, and rs2236212 in ELOVL2 gene were detected by Sanger sequencing.

Results: Stratified by gender, the genotypes and allele frequencies of rs3798719, rs1570069 and rs2236212 showed significant differences between the two groups (χ2 = 6.987, P = 0.030), Genetic modeling showed that rs3798719 was statistically different in the overdominance model (χ2 = 4.784, OR = 1.414, 95% CI: 1.036-1.929, P < 0.05). The polymorphism of rs2236212 between male TB patients and healthy controls was statistically different in the dominance model. (χ2 = 4.192, OR = 0.507; 95% CI: 0.262-0.981, P < 0.05).

Conclusion: The rs3798719 of ELOVL2 gene may be associated with susceptibility to TB in female population and the rs2236212 of ELOVL2 gene may be associated with TB incidence in male patients.

1. Global tuberculosis control: surveillance, planning, financing (2017). WHO Report 2018. Geneva: World Health Organiza-tion.
2. Möller M, Hoal EG (2010). Past, present and future directions in human genetic susceptibility to tuberculosis. FEMS Im-munol Med Microbiol, 58:3-26.
3. Wang W, Deng G, Zhang G, et al (2019). Genetic polymorphism rs8193036 of IL17A is associated with increased sus-ceptibility to pulmonary tuberculosis in Chinese Han population. Cytokine, 127:154956.
4. Simopoulos AP (2004). Omega-6 /omega-3 essential fatty acid ratio and chronic dis-eases. Food Rev Int, 20:77-90.
5. Simopoulos AP (2002). The importance of the ratio of omega-6 /omega-3 essential fatty acids. Biomed Pharmacother, 56:365-379.
6. Hibbeln JR, Nieminen LR, Blasbalg TL, et al (2006). Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr, 83:1483S-1493S.
7. Soh AZ, Chee CB, Wang YT, et al (2016). Dietary Cholesterol Increases the Risk whereas PUFAs Reduce the Risk of Ac-tive Tuberculosis in Singapore Chinese. J Nutr, 146:1093-1100.
8. Mateusz C, Monika, T, Michał T (2018).A Comprehensive Review of Chemistry, Sources and Bioavailability of Omega-3 Fatty Acids. Nutrients, 10:pii: E1662.
9. Wu Y, Wang Y, Tian H, et al (2019). DHA intake interacts with ELOVL2 and ELOVL5 genetic variants to influence polyunsaturated fatty acids in human milk. J Lipid Res, 60:1043-1049.
10. Li X, Gan ZW, Ding Z, et al (2017). Genetic Variants in the ELOVL5 but not ELOVL2 Gene Associated with Polyun-saturated Fatty Acids in Han Chinese Breast Milk. Biomed Environ Sci, 30:64-67.
11. Barman M, Nilsson S, Torinsson NÅ, et al (2015). Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Se-rum Polyunsaturated Fatty Acid Compo-sition and Development of Allergy (in a Swedish Birth Cohort). Nutrients, 7:10100-10115.
12. Illig T, Gieger C, Zhai G, et al (2010). A ge-nome-wide perspective of genetic varia-tion in human metabolism. Nat Genet, 42:137-141.
13. Lemaitre RN, Tanaka T, Tang W, et al (2011). Genetic loci associated with plas-ma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium. PLoS Genet, 7:e1002193.
14. Mu M, Wang SF, Sheng J, et al (2014). Die-tary Patterns Are Associated with Body Mass Index and Bone Mineral Density in Chinese Freshmen. J Am Coll Nutr, 32:120-128.
15. Ministry of Health (2012). Diagnostic criteria for pulmonary tuberculosis. Ministry of Health, People’s Republic of China; 2008.
16. Macfarlane DJ, Lee CC, Ho EY, et al (2007). Reliability and validity of the Chinese ver-sion of IPAQ (short, last 7 days). J Sci Med Sport, 10:45–51.
17. Datsomor AK, Zic N, Li K, et al (2019). CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon inhibits elonga-tion of polyunsaturated fatty acids and induces Srebp-1 and target genes. Sci Rep, 9:533.
18. Pauter AM, Olsson P, Asadi A, et al (2014). Elovl2 ablation demonstrates that sys-temic DHA is endogenously produced and is essential for lipid homeostasis in mice. J Lipid Res, 55:718-728.
19. Sun C, Zou M, Wang X, et al (2018). FADS1- FADS2 and ELOVL2 gene pol-ymorphisms in susceptibility to autism spectrum disordersin Chinese children. BMC Psychiatry, 18:283.
20. Pauter AM,-Trattner S, Gonzalez-Bengtsson A, et al (2017). Both maternal and off-spring Elovl2 genotypes determine sys-temic DHA levels in perinatal mice. J Li-pid Res, 58:111-123.
21. Hu Y, Li H, Lu L, et al (2016). Genome-wide meta-analyses identify novel loci as-sociated with n-3 and n-6 polyunsaturat-ed fatty acid levels in Chinese and Euro-pean-ancestry populations. Hum Mol Genet, 25:1215-1224.
22. Cormier H, Rudkowska I, Lemieux S, et al (2014). Effects of FADS and ELOVL polymorphisms on indexes of desaturase and elongase activities: results from a pre-post fish oil supplementation. Genes Nutr, 9:437.
23. Morales E, Bustamante M, Gonzalez JR, et al (2011). Genetic variants of the FADS gene cluster and ELOVL gene family, co-lostrums LC-PUFA levels, breastfeeding, and child cognition. PLoS One, 6: e17181.
24. McFarland CT, Fan YY, Chapkin RS, et al (2008). Dietary polyunsaturated fatty acids modulate resistance to Mycobacterium tuberculosis in guinea pigs. J Nutr, 138: 2123-2128.
25. Jordao L, Lengeling A, Bordat Y, et al (2008). Effects of omega-3 and -6 fatty acids on Mycobacterium tuberculosis in mac-rophages and in mice. Microbes Infect, 10:1379-1386.
26. Anes E, Kühnel MP, Bos E, et al (2003). Se-lected lipids activate phagosome actin as-sembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol, 5:793-802.
27. Bonilla DL, Ly LH, Fan YY, et al (2010). In-corporation of a dietary omega 3 fatty ac-id impairs murine macrophage responses to Mycobacterium tuberculosis. PLoS One, 5:e10878.
28. Paul KP, Leichsenring M, Pfisterer M, et al (1997). Influence of n-6 and n-3 polyun-saturated fatty acids on the resistance to experimental tuberculosis. Metabolism, 46:619-624.
29. Gutierrez MG, Gonzalez AP, Anes E, et al (2009). Role of lipids in killing mycobac-teria by macrophages: evidence for NF-kappa B-dependent and -independent killing induced by different lipids. Cell Mi-crobiol, 11:406-420.
30. Radzikowska U, Rinaldi AO, Çelebi Sözener Z, et al (2019).The Influence of Dietary Fatty Acids on Immune Responses. Nu-trients, 11: pii: E2990..
31. Decoeur F, Benmamar-Badel A, Leyrolle Q, et al (2020). Dietary N-3 PUFA deficiency affects sleep-wake activity in basal condi-tion and in response to an inflammatory challenge in mice. Brain Behav Immun, 85:162-169.
32. Magrum LJ, Johnston PV (1983). Modula-tion of prostaglandin synthesis in rat per-itoneal macrophages with ω-3 fatty acids. Lipids, 18:514-521.
33. Schroit AJ, Gallily R (1979). Macrophage fat-ty acid composition and phagocytosis: ef-fect of unsaturation on cellular phagocytic activity. Immunology, 36:199-205.
34. Rodrigues FG, Campos JB, Silva GD, et al (2016). Endoscopic ultrasound in the di-agnosis of foreign bodies of the colon and rectum. Rev Assoc Med Bras, 62: 818-821.
35. Serhan CN (2014). Pro-resolving lipid medi-ators are leads for resolution physiology. Nature, 510:92-101.
36. Serhan CN, Chiang N, Dalli J, et al (2014). Lipid mediators in the resolution of in-flammation. Cold Spring Harb Perspect Biol, 7:a016311.
37. Williams-Bey Y, Boularan C, Vural A, et al (2014). Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhanc-ing autophagy. PLoS One, 9: e97957. .
38. Li H, Ruan XZ, Powis SH, et al (2005). EPA and DHA reduce LPS-induced inflamma-tion responses in HK-2 cells: evidence for a PPAR-gamma-dependent mecha-nism. Kidney Int, 67: 867-874.
39. Zheng Z, Ge Y, Zhang J, et al (2015). PUFA diets alter the microRNA expression pro-files in an inflammation rat model. Mol Med Rep, 11: 4149-4157.
40. Camuesco D, Gálvez J, Nieto A, et al (2005). Dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyun-saturated fatty acids, attenuates colonic in-flammation in rats with DSS-induced co-litis. J Nutr, 135: 687-694.
41. Kelley DS, Siegel D, Fedor DM, et al (2009). DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr, 139:495-501.
IssueVol 50 No 11 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v50i11.7580
Tuberculosis; ELOVL2 gene Single nucleotide polymorphism China

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Mu M, Jing L, Zou Y-J, Tao X-R, Wang F, Lu J. Polymorphisms of Fatty Acid Elongase 2 Gene Afftects Risk of Pulmonary Tuberculosis in China Han Population. Iran J Public Health. 2021;50(11):2254-2262.