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Leishmaniasisa parasitic disease that affects humans and animals, is mainly transmitted from one host to another through the bite of an infected phlebotomus sand fly vector.Theaim of this study is to evaluate the mechanism of immune-pathogenesis of leishmaniasis, and to determine a possible role for genetic polymorphism in selected gene on the susceptibility to leishmaniasis among Iraqi patients.The present study enrolled a total of 116 subjects in a case-control study design (58 patients with Cutaneous Leishmaniasis and 58 apparently healthy subjects of serving as a control group) for a period from May 2020 to February 2021,all patients 58 in this study were referred and diagnosed clinically in the dermatology outpatient clinic in the Babylon hospital, Iraq. Blood samples were taken from all subjects in the study forepidemiologic,immunological, and genetic study.The resultsofImmunological analysis results show median levels of serum MIFin patients with Cutaneous Leishmaniasis were higher than the median levels of control groups, 5.89 (2.64) pg/ml versus 3.09 (0.98) pg/ml, the difference was highly significant (P < 0.001). Median levels of serum Granzymes Bin patients with Cutaneous Leishmaniasis were higher than the median levels of control groups, 31.22 (16.01) pg/ml versus 15.98 (5.35) pg/ml, the difference was highly significant (P < 0.001). Median serum level of CAMP LL37 in patients with Cutaneous Leishmaniasis was 8.39 (6.19) pg/ml, while that of control groups was 4.83 (1.04) pg/ml.Hence serum level of CAMP LL37 was significantly higher in patients with Cutaneous Leishmaniasis than control group (P < 0.001).PCR-RFLP for TOLLIP polymorphism Hardy Weinberg equation was applied to node genotypes, CC, CT and TT, distribution within the control group and results are showed the homozygous wild genotype CC was encountered in 37 out of 50 control subjects; the heterozygous CT genotype was seen in 9 out of 50 control subjects and the homozygous mutant TT genotype was seen in 4 out of 50 control subjects, . Individuals homozygous for rs3750920 T allele had three times risks of developing CL compared to individuals homozygous for the rs3750920 C allele (P =< 0.001 ; OR, 2.62 [95% CI 1.48 - 4.63]). The current study showed that polymorphism is associated with CL we foundcommon genetic variants of TOLLIP gene (rs3750920) that are associated with cutaneous leishmaniasis susceptibility, these genetic markers were associated with an increased risk for developing CL in a case-population study in Iraq and it is the first study deals with the genetic polymorphism of TOLLIP gene in endemic areas in Iraq.