title: Single-point haplotype scores telomeric to human leukocyte antigen-C give a high susceptibility major histocompatibility complex haplotype for psoriasis in a Caucasian population.
abstract: Psoriasis is a chronic inflammatory skin disease that affects 0.1%-5% depending on the population. PSORS1 is the major susceptibility locus, accounting for approximately 33%-50% of the genetic component of psoriasis among Caucasians. PSORS1 is located within the major histocompatibility complex (MHC) locus on 6p21.3. Its position has been refined to hundreds of kilobase and the region located at approximately 100-200 kb telomeric to human leukocyte antigen (HLA)-C is a very strong candidate. To determine the MHC psoriasis risk haplotype, we screened the whole 46 kb interval for single-nucleotide polymorphisms (SNP) and identified 138 SNP. We genotyped 29 SNP throughout this region in psoriatic nuclear families. We calculated the frequency of haplotypes generated by the 29 SNP using all genotyped founder individuals and found four common haplotype with frequency >0.10. We then used SNPtagger to derive the best six SNP and fed these into Transmit using 148 nuclear families. We found that CTGGAC haplotype is a single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27 (p<0.0001). Most importantly the six selected SNP accurately tagged the most common haplotype found in this region. Moreover, using the same program (Transmit) we show that the association with CTGGAC is higher than the one with HLA-Cw6 (chi2=10.53; p=0.0051). Our results give scores as high as the highest single-point scores suggesting that it is unlikely to be able to discriminate the origin of the association on this analysis on strength of association.
authors.affiliation: Oxagen Limited, Abingdon, Oxon, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Lench
authors.forename: Mark M
authors.initials: MM
authors.lastname: Iles
authors.forename: Ian
authors.initials: I
authors.lastname: Mackay
authors.forename: Ramila
authors.initials: R
authors.lastname: Patel
authors.forename: Gurdeep S
authors.initials: GS
authors.lastname: Sagoo
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Ward
authors.forename: Bryan
authors.initials: B
authors.lastname: Dechairo
authors.forename: Mark
authors.initials: M
authors.lastname: Olavesen
authors.forename: Alisoun
authors.initials: A
authors.lastname: Carey
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Duff
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cork
authors.forename: Rachid
authors.initials: R
authors.lastname: Tazi-Ahnini
mesh_terms: D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D015236:HLA-C Antigens