Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL-12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic dermatitis in Koreans.
BACKGROUND
The acute skin lesions of atopic dermatitis (AD) are associated with Th2 cells; however, the chronic skin lesions of AD are associated with Th1 cells via the action of IL-12.


OBJECTIVE
We evaluated the associations of single nucleotide polymorphisms (SNPs) and haplotype in the IL-12 and IL-12 receptor genes, and determined the gene-gene interactions between the SNPs of these genes and the SNPs of the IL-18 gene that we previously reported.


METHODS
We genotyped 24 SNPs from 4 IL-12/IL-12R genes for 1089 case-control samples (631 AD patients and 458 normal controls). We measured the serum IL-12 concentrations in 89 individuals (79 AD patients and 10 controls) by ELISA. We analyzed the SNPs and haplotypes in each gene and also searched for the gene-gene interactions.


RESULTS
The rs582504 (IVS-798A/T) SNP and the haplotype TA (rs582054 and rs2243151) in the IL-12A gene, and the rs438421 (IVS12+1266T/C) SNP and the haplotype CCA (rs375947, rs438421, and rs1870063) in the IL-12RB1 gene were significantly associated with the AD phenotype. We showed that the rs438421 polymorphism in the IL-12RB1 (TT) gene and the rs2066446 polymorphism in the IL-12RB2 (AA) gene had a significant interaction to develop the ADe phenotype (allergic type of AD), and those individuals with the risk alleles, TT/AA/CC (IL-12RB1/IL-12RB2/IL-18), have more than a 10-fold increased risk to develop ADe.


CONCLUSIONS
This study provides evidence for a significant interaction between the IL-12RB1 and IL-12RB2 genes that contribute to a 4-fold increased risk for developing ADe. In addition to the IL-12R interaction, we suggest that the IL-18 gene can significantly interact with the IL-12R gene to develop ADe. In addition to the interaction, the SNPs and haplotypes in the IL-12A and IL-12RB1 genes are independently and significantly associated with the AD phenotype, and especially with the ADe phenotype. This data may contribute to our understanding of AD genetic interactions and account for the additional risk of certain patients to develop AD.
Namkung
Jung-Hyun
JH
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea.
Lee
Jong-Eun
JE
Kim
Eugene
E
Kim
Song
S
Kim
Sook
S
Shin
Eun-Soon
ES
Cho
Eun-Young
EY
Yang
Jun-Mo
JM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001772:Blood Cell Count; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics*; D004804:Eosinophils; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007223:Infant; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D056910:Republic of Korea; D055815:Young Adult
D020382:Interleukin-18; D053707:Receptors, Interleukin-12; D018664:Interleukin-12