Leprosy and the adaptation of human toll-like receptor 1.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

Association study of major risk single nucleotide polymorphisms in the common regulatory region of PARK2 and PACRG genes with leprosy in an Indian population.

Single nucleotide polymorphisms (SNPs) in the regulatory region shared by PARK2 and PACRG have been identified as major risk factors for leprosy susceptibility in two ethnically distinct populations. We investigated the association of six SNPs present in this regulatory region with leprosy susceptibility in an Indian population. Genotyping was performed by direct PCR sequencing in 286 leprosy patients and 350 healthy controls. Our results showed that T allele of SNPs PARK2_e01 (-2599) and 28 kb target_2_1 was significantly associated with susceptibility to leprosy per se (P=0.03 and 0.03, respectively). The T allele of SNPs PARK2_e01 (-2599) showed a significant recessive effect (P=0.04) in susceptibility to leprosy in Indian population as against the dominant effect of haplotype T-C of the major risk SNPs PARK2_e01 (-2599) and rs1040079 in Brazilian and Vietnamese population. However, after bonferroni corrections, these significant differences disappeared. Haplotype analysis also showed a lack of significant association of any haplotype with cases or controls. The noninvolvement of major risk SNPs in the regulatory region of PARK2 and PACRG locus with leprosy susceptibility in Indian population highlights the differential effect of these SNPs in regulating genetic susceptibility to leprosy in different populations.

Cardio-facio-cutaneous syndrome: report of a case with a review of the literature.

A sporadic case of cardio-facio-cutaneous syndrome occurring in an 18-year-old girl is reported, with a brief review of pertinent literature, for its rarity and clinical interest. She had a characteristic cranio-facial appearance, a wide range of ectodermal defects, dystrophic nails and teeth, palmo-plantar keratoderma, typical short, coarse, unruly hair, pulmonic stenosis and mild mental retardation. She had no history of consanguinity and genetic studies did not reveal any abnormality.

Efficacy of hydroquinone (2%) versus tretinoin (0.025%) as adjunct topical agents for chemical peeling in patients of melasma.

BACKGROUND AND OBJECTIVES: In recent years, chemical peels have become increasingly popular in the treatment of melasma. However, postpeel hyperpigmentation is a frequently encountered side effect, especially in dark-skinned individuals. The role of priming agents in preventing this complication has not been adequately evaluated. Hence, we studied the effect of hydroquinone versus tretinoin as priming agents in minimizing the incidence of this side effect in a double-blind, randomized clinical trial of 50 patients with melasma. METHODS: Of a total of 50 patients, 25 patients each with a similar skin phototype, the nature and severity of melasma were assigned to groups I and II. The patients were primed with 2% hydroquinone in group I, and in group II with 0.025% tretinoin once daily (night time) 2 weeks before starting trichloroacetic acid peels. Subsequently, all of them received trichloroacetic acid peels at intervals of 2 weeks for 12 weeks, followed by monthly peels for next 12 weeks during the follow-up period. Patients continued to use a sunscreen with an SPF of greater than 15 and the recommended priming agent during the follow-up. Final assessment was made at 6 months, based on the impression of the patient, clinical examination by the physician, and photographic analysis. RESULTS: A total of 50 patients (25 in each group) participated in the study. The predominant Fitzpatrick skin type observed among them was type IV (56%), and the type of melasma was mixed (44%). The final results at 12 weeks were comparable in two groups. However, a significant difference was seen in the two groups during the follow-up period, with continued improvement in 24% and worsening in 28% of patients in group I and continued improvement in only 16% and worsening in 40% in group II patients. CONCLUSIONS: Hydroquinone is superior to tretinoin as a priming agent in maintaining the results achieved with peels and in decreasing the incidence of postpeel reactive hyperpigmentation.