Esma Čečuk-Jeličić

A new extended haplotype Cw*0602-B57-DRB1+0701-DQA1*0201-DQB1+0201 associated with psoriasis in the Croatian population

In this study, we have analysed the distribution of HLA class II alleles and the extended haplotype HLA‐Cw‐B‐DRB1‐DQA1‐DQB1 in Croatian patients with type I and type II psoriasis by hybridization with specific oligonucleotide probes. Type I psoriasis showed a significant association with the DRB1*0701 [P < 0.00001; relative risk (RR) = 5.83], DQA1*0201 (P < 0.00001; RR = 6.12), DQB1*0201 (P = 0.0006; RR = 3.29) and DQB1*0303 alleles (P = 0.0008; RR = 7.51). A negative correlation with type I disease was observed for the DQA1*0102 allele (P = 0.002; RR = 0.26). Type II psoriasis did not show any association with any class II alleles. The extended haplotype HLA‐Cw*0602‐B57‐DRB1*0701‐DQA1*0201‐DQB1*0201 was present at a significantly higher frequency in type I patients (P < 0.00001; RR = 7.72). However, this haplotype was not detected at all in patients with type II psoriasis. In conclusion, the extended haplotype HLA‐Cw*0602‐B57‐DRB1*0701‐DQA1*0201‐DQB1*0201 is a risk haplotype for type I disease in the Croatian population. This particular haplotype has not been reported previously in association with psoriasis in any other ethnic groups.

HLA-B27 subtypes in Croatian patients with ankylosing spondylitis

Sir, The association between ankylosing spondylitis (AS) and HLA-B27 is one of the strongest known and it has been con® rmed in various populations. HLAB27 is found in about 96% of AS patients, while only 4 ± 12% of healthy Caucasians are HLA-B27 positive (1). The study of the association between B27 subtypes and AS gave different results in various populations. The results available indicate that alleles B*2701, *2702, *2704, *2705, and *2707 are occurring in AS patients (1,2). Negative association of B*2706 and *2709 subtypes has been described in patient groups of the Thai and Sardinian population, respectively (2). The frequency of the B27 antigen in healthy Croatians is about 12%, while in AS patients it is approximately 90%. The aims of the study was to analyse the distribution of HLA class I antigens and B27 haplotypes in a group of 119 B27+ AS patients and a group of 165 B27+ healthy individuals, and to examine the frequency of B27 subtypes in B27+ AS patients and B27+ healthy controls. A total of 119 unrelated B27+ AS patients and 165 B27+ healthy individuals were included in this study. For all individuals HLA genotyping was performed using segregation data of parental haplotypes. The AS patients were clinically diagnosed according to the New York criteria of 1986. All the included families had been living in the same area for three generations at least. HLA-A and -B typing was performed using the standard microlymphocytotoxity test (MLCT) on local trays (3). PCR-SSP typing for the B27 subtypes was performed using Dynal HLA-B27 high resolution kit (DYNAL, Oslo, Norway) (4). Comparison of HLA class I antigen frequencies between both B27+ groups (AS patients and B27+ healthy individuals) and random controls, revealed an increased frequency of HLA-B44 antigen in random healthy controls (p= 0.65 and p= 0.59, respectively). Results of HLA-A and -B antigen frequencies showed a quite similar distribution in both B27+ groups. An increased frequency of HLAA9 antigen, observed among Basque, Indian, and USA AS patients, was not found in Croatian AS patients (9.1% vs 8.8%, p40.05) (5). In this study we did not observe HLA-B60 antigen more often than expected in B27+ AS patients as was suggested by Robinson et al (2.8% vs 3.9%, p40.05). Namely, they reported that B60 increases susceptibility to AS in B27+ patients while it does not seem to be a predisposing factor in the absence of B27 antigen (6). Our results indicate that there are no additional HLA-B alleles that are involved in a synergistic effect with B27 in a population of Croatian AS patients. This lack of agreement about association between AS and other HLA class I alleles could be explained by genetic characteristic of each population reported, but also support the hypothesis that B27 itself is a major genetic susceptibility factor for AS. The ® nding of lower frequency of the HLA-A26, -B27 haplotype in the group of AS patients in comparison to B27+ healthy controls (2.0% vs 5.9%,p50.05) suggest the potentially protective role of this haplotype in the Croatian AS population. This hypothesis needs to be con® rmed on a larger group of patients bearing B27 haplotypes. Molecular typing of HLA-B27 subtypes was performed in a group of 45 unrelated AS patients and in a group of 38 B27+ healthy controls. The Croatian population showed quite similar distribution of B27 subtypes as in other Caucasians reported so far (1). AS patients possessed similar B27 subtypes as B27+ control individuals. The B*2705 allele was the most common allele in AS patients and B27+ controls (83.3% and 73.7%, respectively), while B*2702 was the second most common allele in both groups (12.5% and 23.7%, respectively). The data from different populations suggest that both B*2702 and B*2705 are positively associated with AS (1,2). The other two subtypes observed in Croatian AS patients, B*2701 and B*2704, are previously reported as alleles associated with AS. B*2704 subtype is positively associated with AS in Oriental populations but its presence is also reported in the Mary population, a Finno-Ugric population from Russia. Thus, it seems that this allele is not only present in Orientals, as was suggested by Lopez-Larrea and further supported by this study (2). At this moment it is not possible to make conclusion for positive or non-association between B*2701 and AS because the publishing data are based on a small number of AS patients. Present study did not demonstrate any of B27 alleles as susceptible or protective genetic marker for AS in the Croatian population and it ® ts into the frame of the oldness of the association between AS Zorana Grubic , National Referral Organ Transplantation and Tissue Typing Center, University Hospital Center Zagreb, KisÏ patic eva 12, HR-10000, Zagreb, CroatiaA total of 119 unrealted B27+ AS patients and 165 B27+ healthy controls were included in this study. For all individuals HLA genotyping was performed using segregation data of parental haplotypes. The AS patients were clinically diagnosed according to the New York criteria of 1986. HLA-A and -B typing was performed using the standard MLCT test on local trays. PCR-SSP typing for the B-27 subtypes was performed using Dynal HLA-B27 high resolution kit. Present study did not demonstarte any of B27 alleles as susceptible or protective genetic marker for AS in the Croatian population and it fits into the frame of the oldness of the association between AS and B27. AS appears to be older than the origin of the B27 subtypes.