Tissue inhibitor of metalloproteinase-1 (TIMP-1) serum level and genetic polymorphisms associated with cutaneous leishmania infections

Abstract

IntroductionCutaneous leishmaniasis is considered a parasitic contagion resulting from the flagellated parasite belonging to the genus of Leishmania. Also, cutaneous leishmaniasis is a zoonotic ailment transmitted through the bloodsucking sand-flies bite (belonging to the Phlebotomus genus). The disease's reservoirs included wild or semi-domesticated animals, in general rodents and dogs. Tissue inhibitor metalloproteinase-1 (TIMP-1) is one of the extracellular matrix proteins that have a role in vessel wall degeneration and aneurysm development. In addition, it belongs to the zinc-dependent endopeptidases family that are involved in the degradation of connective tissues proteins which are included in vascular integrity maintenance. The Genetic deviations in the TIMP-1 genes might impact their expression at the transcription level or the enzyme activity. Therefore, the present study aimed to detect the impact of TIMP-1 serum level and single nucleotide polymorphisms (SNPs) rs41454248 and rs1043428 among the cutaneous leishmaniasis patients’ group compared to the control group. SubjectsSeventy-five cutaneous leishmaniasis patients (39 males and 36 females) with the age mean 23.91 ± 13.14 years participated in this study, compared to the matched number, age, and gender of a healthy control group (75: 38 males and 37 females) with the age mean 22.84 ± 4.35 years. In the current study, the serum level of TIM-1 and rs41454248 and rs1043428 SNPs were studied among the cutaneous leishmaniasis patients’ group compared to the control group. ResultsThe findings of the TIMP-1 level referred to a significant decrease among the cutaneous leishmaniasis patients’ group compared to the healthy control group (26339.67 ± 900.79 vs. 33480.25 ± 1098.63). Such, the rs41454248 SNPs findings referred that the GG genotype and G allele were non-significantly increased frequency percentage in cutaneous leishmaniasis patients group compared to the healthy control group (29.33 vs. 18.67%, OR: 1.81, p = 0.180; 55.0 vs. 47.0%, OR: 1.38, p = 0.204 respectively). Also, the high OR value of GG genotype and G allele referred to this genotype and allele might be a risk factor for cutaneous leishmaniasis. Likewise, the findings of rs1043428 SNPs appeared that the CC genotype and C allele were significantly increased frequency percentage in cutaneous leishmaniasis patients' group compared to the control group (37.33 vs. 4.0%, OR: 14.30, p = 3.6 × 10−7; 57.0 vs. 21.33, OR: 4.82, p = 4.5 × 10−10). Also, the high OR value of CC genotype and C allele referred to this genotype and allele might be risk factors for cutaneous leishmaniasis. In addition, the CG genotype appeared a non-significant increased frequency percentage in the patients' group compared to the control group and the value of OR referred to might be a risk factor for cutaneous leishmaniasis (33.33 vs. 25.33, OR: 1.47, p = 0.370). In addition, the serum level of TIMP-1 with the rs41454248 was significantly decreased in GA and AA genotypes of the patients’ group compared to the control. While the level was non-significantly decreased in the GG genotype of the patients' group compared to the control group. Likewise, the level of TIMP-1 with the rs1043428 was non-significantly decreased in all genotypes (except TT genotype) of the patients' group compared to the control. Whereas, a significant decrease level was appeared in the TT genotype of the patients' group compared to the healthy control group. ConclusionThe current findings demonstrated a significant association between TIMP-1 serum level and genetic polymorphisms (rs1043428 and rs41454248) among cutaneous leishmaniasis patients.