Association of IL12B risk haplotype and lack of interaction with HLA-Cw6 among the psoriasis patients in India.
Psoriasis is a complex multifactorial chronic inflammatory skin disorder involving both genetic and environmental susceptibility factors. It is strongly associated with HLA-Cw6, but several studies suggested that further genetic factors may confer additional risk. We investigated the association of two single-nucleotide polymorphisms (SNPs), rs3212227 at the 3'-untranslated region and rs7709212 located at ~6.7 kb upstream from the transcription start site of IL12B gene in a case-control study comprising 1702 individuals from India. We found both SNPs were significantly associated with psoriasis (rs7709212: odds ratio (OR)=1.37, P-value=1.09 × 10-5; rs3212227: OR=1.38, P-value=8.88 × 10-6). IL12B gene was significantly upregulated in involved skin of psoriasis patients with risk genotype carriers (rs7709212_TT and rs3212227_TT) compared with non-risk genotype carriers (rs7709212_CC and rs3212227_GG). Significantly higher serum protein concentration of IL12 was also observed among risk allele carriers compared with non-risk allele carriers irrespective of the presence of HLA-Cw6 allele. Haplotype analysis suggested significant increased risk (OR=1.50, P-value=5.01 × 10-8) to the disease when both risk alleles of IL12B were present. IL12 serum protein concentration of risk haplotype (TT-TT) carriers showed significant upregulation compared with the non-risk carriers independent of HLA-Cw6 alleles. Our data suggested the association of IL12B with the psoriasis, however no evidence was observed for the epistatic effect of IL12B with HLA-Cw6 among the psoriasis patients in India.
Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
Aditi
A
Chandra
Consultant Dermatologist, Uttarpara, Hooghly, India.
Swapan
S
Senapati
Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
Saurabh
S
Ghosh
Department of Dermatology, SSKM Hospital, Kolkata, India.
Gobinda
G
Chatterjee
Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
Raghunath
R
Chatterjee
D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007194:India; D053762:Interleukin-12 Subunit p40 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012306:Risk; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D020413:3' Untranslated Regions; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40