title: Association study of major risk single nucleotide polymorphisms in the common regulatory region of PARK2 and PACRG genes with leprosy in an Indian population.
abstract: 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.
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, Lok Nayak Jai Prakash Hospital, New Delhi-110067, India.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Malhotra
authors.forename: Katayoon
authors.initials: K
authors.lastname: Darvishi
authors.forename: Manmohan
authors.initials: M
authors.lastname: Lohra
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
authors.forename: Chander
authors.initials: C
authors.lastname: Grover
authors.forename: Soni
authors.initials: S
authors.lastname: Sood
authors.forename: Belum S N
authors.initials: BS
authors.lastname: Reddy
authors.forename: Ramesh N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D007918:Leprosy / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein