Association of TNF, MBL, and VDR polymorphisms with leprosy phenotypes.
Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes, these findings have not been extensively validated. We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of seven polymorphisms, including a promoter region variant in TNF (G -308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI). We observed an association between TNF -308A and protection from leprosy with an odds ratio of 0.52 (95% confidence interval = 0.29-0.95, p = 0.016). MBL polymorphism G161A was associated with protection from lepromatous leprosy (odds ratio = 0.33, 95% confidence interval = 0.12-0.85, p = 0.010). VDR polymorphisms were not associated with leprosy phenotypes. These results confirm previous findings of an association of TNF -308A with protection from leprosy and MBL polymorphisms with protection from lepromatous leprosy. The statistical significance was modest and will require further study for conclusive validation.
Sapkota
Bishwa R
BR
Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal.
Macdonald
Murdo
M
Berrington
William R
WR
Misch
E Ann
EA
Ranjit
Chaman
C
Siddiqui
M Ruby
MR
Kaplan
Gilla
G
Hawn
Thomas R
TR
D000328:Adult; D004252:DNA Mutational Analysis; D004893:Erythema Nodosum; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007918:Leprosy / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D009390:Nepal; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D037601:Mannose-Binding Lectin; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha