SPR1 gene near HLA-C is unlikely to be a psoriasis susceptibility gene.
Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV.
Chang
Y T
YT
Department of Dermatology, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan.
Tsai
S F
SF
Lin
M W
MW
Liu
H N
HN
Lee
D D
DD
Shiao
Y M
YM
Chin
P J
PJ
Wang
W J
WJ
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006023:Glycoproteins; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D012307:Risk Factors
C109656:CDSN protein, human; D055233:Cornified Envelope Proline-Rich Proteins; D006023:Glycoproteins; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins