Rs2234237 (Thr25Ser) Polymorphism in Patients with Cutaneous Leishmaniasis Caused by : A Case-Control Study in the State of Amazonas, Brazil

Background: Leishmaniasis is an infectious disease caused by parasites. A Th1 immune response is necessary in the acute phase to control the pathogen. The triggering receptor expressed on myeloid cells (TREM)-1 is a potent amplifier of inflammation. Our aim is to identify whether the variant rs2234237 A/T (Thr25Ser) is associated with the disease development of cutaneous leishmaniasis (CL) in -infected individuals. The effects of the rs2234237 genotypes on plasma cytokines IL-1β, IL-6, IL-8, IL-10, MCP-1 and TNF-α are also investigated.

Methods: 838 patients with CL and 818 healthy controls (HCs) living in the same endemic areas were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Plasma cytokines were assayed in 400 patients with CL and 400 HCs using the BioPlex assay.

Results: The genotypes' and alleles' frequencies were similar in both patients with CL (AA = 618, 74%; AT = 202, 24%; TT = 18, 2%) and in HCs (AA = 580, 71%; AT = 220, 27%; TT = 18, 2%). Rs2234237 showed a modest effect on plasma IL-10 that disappeared when correction of the -value was applied. Plasma IL-10 by rs2234237 genotypes were (mean ± SEM; AA = 2.91 pg/mL ± 0.14; AT = 2.35 pg/mL ± 0.12; TT = 3.14 pg/mL ± 0.56; = 0.05).

Conclusion: The rs2234237 (Thr25Ser) seems to have no influence on the susceptibility or resistance to infections.

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References

Sacks D, Noben-Trauth N . The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002; 2(11):845-58. DOI: 10.1038/nri933. View

von Stebut E, Udey M . Requirements for Th1-dependent immunity against infection with Leishmania major. Microbes Infect. 2004; 6(12):1102-9. DOI: 10.1016/j.micinf.2004.05.024. View

Strimmer K . fdrtool: a versatile R package for estimating local and tail area-based false discovery rates. Bioinformatics. 2008; 24(12):1461-2. DOI: 10.1093/bioinformatics/btn209. View

Jung E, Kim S, Moon C, Shin D, Son N, Kim E . Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and inflammatory bowel diseases in the Korean population. Life Sci. 2011; 89(9-10):289-94. DOI: 10.1016/j.lfs.2011.06.018. View

Weber B, Schuster S, Zysset D, Rihs S, Dickgreber N, Schurch C . TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance. PLoS Pathog. 2014; 10(1):e1003900. PMC: 3894224. DOI: 10.1371/journal.ppat.1003900. View

Fortin C, Lesur O, Fulop Jr T . Effects of TREM-1 activation in human neutrophils: activation of signaling pathways, recruitment into lipid rafts and association with TLR4. Int Immunol. 2006; 19(1):41-50. DOI: 10.1093/intimm/dxl119. View

Gonzalez J, Armengol L, Sole X, Guino E, Mercader J, Estivill X . SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007; 23(5):644-5. DOI: 10.1093/bioinformatics/btm025. View

Buckland K, Ramaprakash H, Murray L, Carpenter K, Choi E, Kunkel S . Triggering receptor expressed on myeloid cells-1 (TREM-1) modulates immune responses to Aspergillus fumigatus during fungal asthma in mice. Immunol Invest. 2011; 40(7-8):692-722. PMC: 5540193. DOI: 10.3109/08820139.2011.578270. View

Ornatowska M, Azim A, Wang X, Christman J, Xiao L, Joo M . Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages. Am J Physiol Lung Cell Mol Physiol. 2007; 293(6):L1377-84. PMC: 3969455. DOI: 10.1152/ajplung.00140.2007. View

10.

Polari L, Carneiro P, Macedo M, Machado P, Scott P, Carvalho E . Infection Enhances Toll-Like Receptors 2 and 4 Expression and Triggers TNF-α and IL-10 Production in Human Cutaneous Leishmaniasis. Front Cell Infect Microbiol. 2019; 9:120. PMC: 6507514. DOI: 10.3389/fcimb.2019.00120. View

11.

Bleharski J, Kiessler V, Buonsanti C, Sieling P, Stenger S, Colonna M . A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol. 2003; 170(7):3812-8. DOI: 10.4049/jimmunol.170.7.3812. View

12.

Golovkin A, Ponasenko A, Khutornaya M, Kutikhin A, Salakhov R, Yuzhalin A . Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population. Gene. 2014; 550(1):101-9. DOI: 10.1016/j.gene.2014.08.022. View

13.

Su L, Liu C, Li C, Jiang Z, Xiao K, Zhang X . Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation. 2012; 35(6):1833-43. DOI: 10.1007/s10753-012-9504-z. View

14.

Burza S, Croft S, Boelaert M . Leishmaniasis. Lancet. 2018; 392(10151):951-970. DOI: 10.1016/S0140-6736(18)31204-2. View

15.

Runzheimer J, Mewes C, Buttner B, Hinz J, Popov A, Ghadimi M . Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients-A Monocentric Prospective Genetic Association Study. J Clin Med. 2019; 8(3). PMC: 6463065. DOI: 10.3390/jcm8030301. View

16.

Garcia L, Kindt A, Bermudez H, Llanos-Cuentas A, De Doncker S, Arevalo J . Culture-independent species typing of neotropical Leishmania for clinical validation of a PCR-based assay targeting heat shock protein 70 genes. J Clin Microbiol. 2004; 42(5):2294-7. PMC: 404633. DOI: 10.1128/JCM.42.5.2294-2297.2004. View

17.

Chen Q, Zhou H, Wu S, Wang H, Lv C, Cheng B . Lack of association between TREM-1 gene polymorphisms and severe sepsis in a Chinese Han population. Hum Immunol. 2008; 69(3):220-6. DOI: 10.1016/j.humimm.2008.01.013. View

18.

Adukpo S, Gyan B, Ofori M, Dodoo D, Velavan T, Meyer C . Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine gene variants in complicated and uncomplicated malaria. Trop Med Int Health. 2016; 21(12):1592-1601. DOI: 10.1111/tmi.12787. View

19.

Peng L, Li J, Zhou G, Deng L, Yao H . Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population. World J Emerg Med. 2015; 6(2):123-30. PMC: 4458472. DOI: 10.5847/wjem.j.1920-8642.2015.02.007. View

20.

Tessarz A, Cerwenka A . The TREM-1/DAP12 pathway. Immunol Lett. 2008; 116(2):111-6. DOI: 10.1016/j.imlet.2007.11.021. View