Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families.

HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

Psychosocial factors and smoking as risk factors in lung carcinoma.

In a retrospective study as part of a larger study 419 male patients with bronchial carcinoma were questioned by means of a 'biographical questionnaire' concerning their life history, their personality, and their approach to life. Furthermore questions with regard to their smoking habits (tobacco smoke condensate exposure) were asked. Only patients who smoked cigarettes regularly were involved in the interrogation and the results were compared with those of smoking healthy controls and patients with non-malignant lung diseases (N = 162). For each pair group-controls a discriminant analysis was carried out. By reclassification a correct assignment of approx. 62% in each case could then be obtained. In addition, the answer pattern of the carcinoma patients was compared with a group of patients with non-malignant lung diseases. The results obtained were similar to those of the comparison with the healthy control group.