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- Title
hRDH-E2gene polymorphisms, variable transcriptional start sites, and psoriasis.
- Authors
Matsuzaka, Yasunari; Okamoto, Koichi; Yoshikawa, Yoko; Takaki, Asumi; Oka, Akira; Mabuchi, Tomotaka; Iizuka, Mariko; Ozawa, Akira; Tamiya, Gen; Kulski, Jerzy; Inoko, Hidetoshi
- Abstract
hRDH-E2 is a member of the short-chain alcohol dehydrogenase/reductase (SDR) family that converts retinol to retinaldehyde as the first and rate-limiting step in the retinoic acid synthetic pathway. This pathway is critical for the maintenance of epidermal homeostasisin vivo. Previously, we reported that the mRNA levels ofhRDH-E2in psoriatic skin were elevated significantly compared with that in healthy individual skin and psoriatic unaffected skin. The gene encoding hRDH-E2 is located on Chromosome 8 close to a candidate region for psoriasis and therefore is a functional and positional candidate for this disorder. In the present study, the transcription start sites forhRDH-E2gene transcription in the lung were found to be more upstream of those that were identified previously in keratinocytes. Consequently, differences in the nucleotide sequence were determined for all of the coding exons, untranslated regions, and at least 2850 bp of 5'-noncoding sequence ofhRDH-E2by direct sequencing of polymerase chain reaction (PCR)-amplified DNA samples obtained from 8 psoriatic patients and 8 healthy controls. One polymorphic microsatellite marker at the noncoding 3' end of the gene and six single nucleotide polymorphisms (SNPs) (three in the 5' flanking sequence, two in the coding sequence, and one in the intronic sequence) were identified. One of the SNPs was nonsynonymous in the second exon with an allelic variation between the amino acid sequences Arg and Trp. The microsatellite marker and the six SNPs were all genotyped in 100 Japanese psoriatic patients and 120 controls. However, there were no statistically significant differences in the genotype or allele frequency distributions between the cases and controls. On this basis, we conclude that the polymorphisms that we detected for thehRDH-E2gene do not contribute to the etiology of psoriasis but may be important in diseases of other tissues.
- Subjects
ALCOHOL dehydrogenase; SKIN diseases; NUCLEOTIDE sequence; NUCLEOTIDE analysis; RETINAL (Visual pigment); GENETIC research
- Publication
Mammalian Genome, 2004, Vol 15, Issue 8, p668
- ISSN
0938-8990
- Publication type
Article
- DOI
10.1007/s00335-004-2349-5