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Objective To analyze the effect of clinical, biochemical factors, and Mannose Binding Lectin 2 (MBL2) gene variations on medical management in filarial chyluria (FC) patients. Material and methods We conducted a study between March 2013 and April 2016. MBL2polymorphisms were genotyped in confirmed 101 medically-treated cases of FC. Demographic, clinical, and biochemical variables were compared between remission and failure groups. Genotyping of MBL2 codon 54 and promoter -221 were undertaken by polymerase chain reaction. Genotype frequencies were compared with clinical and biochemical variables and medical treatment outcomes (remission/failure). The association between genotypes and treatment response was estimated by OR and 95% CI and generated by the chi-square test. Results The mean age was 36.9±10.28-years and the male-female ratio was 3:1.2. Sixty-six patients had remission (Group-A) while 35 had recurrence (Group-B) at a mean follow-up of 21 months. The success rate for medical therapy was 65.35%. There was no statistical difference observed in the demographic profile of the two groups. On multivariate analysis, patients in Group-B had a higher grade of chyluria (p=0.005), had experienced greater number of disease attacks in the past (p=0.022), and had higher urinary triglyceride levels (TG) (p<0.001) as compared to Group-A patients. A significant association of MBL2 codon 54 genotypes was observed with the recurrent presentation of chyluria (p=0.044), grade of chyluria (p=0.028), and urinary TGs (p=0.001). However, genotype distribution at -221 did not show association with clinical and biochemical parameters of FC patients. The distribution of genotypes at codon 54 differed significantly between remission and failure/recurrence group; the variant genotype BB was significantly higher in the recurrence or failure group (OR:6.00; 95%CI, 1.00-35.91; p=0.050). However, frequencies of variant genotype YX and recessive group YX+XX of MBL2 -221 promoter was higher in remission group (OR:2.97;95%CI, 1.23-7.13; p=0.018 and OR:2.76; 95%CI, 1.80-6.50; p=0.020), respectively, showing that genetic variant may be associated with response to medical therapy. Conclusion Higher grade of chyluria, a higher number of disease attacks in the past, and higher urinary TGs levels were clinical predictors of poor response to medical treatment. Our results showed that the variants of MBL2 genes have an impact on treatment outcomes in FC patients. These observations may be limited by sample size.
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INTRODUCTION: Chyluria which is endemic in many parts of the world is mainly caused by Wuchereria bancrofti. CHIT1 (chitotriosidase) is produced by macrophages and plays an important role in the defense against chitin containing pathogen such as filarial parasite. Variation in the coding region with 24 bp duplication allele results in reduced CHIT1 activity that enhance the survival of parasite which may play a role in the occurrence of disease. AIM: To examine the role of 24bp duplication of CHIT1 gene in patients of filarial chyluria (FC). MATERIALS AND METHODS: A case-control study was carried out where 155 confirmed FC patients and equal number of age-, sex- and residence-matched controls without any symptoms or signs of lymphatic filariasis, confirmed by negative immunochromatographic card test (ICT) and IgG/IgM combo rapid antibody test, from a hospital-based population were enrolled. Filarial aetiology was confirmed on the basis of DEC-provocative test (Giemsa staining), ICT and IgG/IgM- antifiarial antibody test. The patients positive by either of these tests were enrolled as FC cases. 24bp duplication in CHIT1 gene in FC was detected by the product size 99bp of amplified gene using polymerase chain reaction. RESULTS: The mean ages of patients and controls were 38.25±12.09 and 35.45±12.53 years, respectively while male: female ratio was 2.4:1. The mean duration of illness in chyluria patients was 62.81±60.83 months and mean number of episodes was 2.54±1.11. Homozygous wild type, heterozygous and homozygous mutant frequencies were 10.3%, 81.3% and 8.4% in FC patients and 18.7%, 75.5%, and 5.8% in controls, respectively. The 24bp duplication in CHIT1 gene showed a significant association in Heterozygous (HT) genotype with Odd Ratio (OR) of 1.95, 95% Confidence Interval (CI) (1.01-3.77); p=0.04. However, the homozygous mutant genotype (TT) was found to be non-significant with OR of 2.61, 95% CI (0.91-7.45); p=0.07. The combination of both HT+TT was also found to be significant with OR of 2.00, 95% CI (1.03-3.85); p=0.03. CONCLUSION: In this study from Northern India, CHIT1 gene polymorphism showed an influence as a possible risk factor for susceptibility to FC. Further studies need to be done on a larger number of FC patients in different regions of the country.