Both DRB4*0101 and DQB1*0303 alleles provide significant susceptibility for vitiligo.

We identified 37 CFTR mutations in 69 well characterized Iranian CF patients, obtaining a CFTR mutation detection rate of 81.9%, the highest detection rate obtained in the Iranian population so far. These findings will assist in genetic counseling, prenatal diagnosis and future screening of CF in Iran.

The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301-DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701-DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.

Several publications have shown that certain alleles at the HLA-DRB1, -DQA1, and -DQB1 loci are associated with insulin-dependent diabetes mellitus (IDDM). Many of these studies have claimed that HLA-DQalpha1Arg52 and DQbeta1Asp57 showed the strongest association with IDDM, but these results could not be confirmed in different populations. We have recently found that DRbeta1Lys71+ provided major susceptibility to IDDM and that DQbeta1Asp57- had an additive effect to DRbeta1Lys71+ [Zamani et al., 1994a: Eur J Hum Genet 2:177-184]. This was confirmed with haplotype analysis in multiplex IDDM families [Zamani et al., 1996a: J Med Genet 33:899-905]. Therefore, we have reanalyzed the data from the literature on the association of the human leucocyte antigen (HLA) DRB1, DQB1, and DQA1 with IDDM in different ethnic groups to determine whether different amino acids in the antigen binding cleft of HLA class II molecules play a preponderant role in the development of IDDM. The results showed that the DRbeta1Lys71+ allele provided the highest relative risk for IDDM in the Belgian, Danish, Greek Taiwanese, and Chinese population while this was not the case in Norwegians, Sardinians, and Algerians. Indeed, in the Sardinian and Algerian population the DRB1*0401 allele encoding Lys71+ is very rare. Nevertheless, the few positive cases were always in the patient group. We also measured the clinical relevance of the testing for DRbeta1Lys71, DQbeta1Asp57, and DQalpha1Arg52 by calculating a prevalence-corrected positive predictive value (PcPPV), a prevalence corrected negative predictive value (PcNPV), the sensitivity and specificity of these tests. The results indicated that the sensitivity of the test for DRbeta1Lys71+ was lower than for DQalpha1Ag52+ and DQbeta1Asp57-, while testing for DRbeta1Lys71+ was more specific than testing for DQbeta1Asp57- and DQalpha1Arg52+ and that the DRbeta1Lys71+ allele had a higher PcPPV than DQalpha1Arg52+ and DQbeta1Asp57- in all studied populations. These results also showed that testing for DRbeta1LyS71+/+ can be useful in IDDM risk assessment particularly in populations with a high prevalence (P) of IDDM such as the Danish (P[IDDM] = 0.65%). PcPPV for DRbeta1Lys71+/+ was 0.2313 in the Danish, indicating a 23.13% risk for an individual who is homozygous for the genotype DRbeta1Lys71+/+ to develop IDDM. Some mechanisms which might explain the role of these HLA class II alleles in susceptibility to IDDM are discussed.

BACKGROUND: Breast cancer cells over-express the adenosine receptor A1 and in most of these cells, P53 gene is a wild type. Because of this fi nding and relationship between A1 receptor and cell apoptosis and proliferation, this study aimed to determine the effect of agonist and antagonist of A1 receptor on cell apoptosis and proliferation and recognize the relationship between this receptor and P53 expression. METHODS: We used a Real-Time PCR test for measuring expression of p53 gene also fl ow cytometry assay for apoptotic and survival cell rate after treatment of MCF-7 cells with A1 receptor agonist CPA (N6-Cyclopentyladenosine) and A1 receptor antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine) in 24,48 and 72 hours. RESULTS: Our fl ow cytometry fi ndings indicate that DPCPX signifi cantly induces apoptosis in MCF-7. Also the expression of P53 becomes upregulated with time of DPCPX treatment. CPA treatment increased the survival cell rate and down-regulated this apoptosis-relevant gene P53 (p > 0.05). CONCLUSION: DPCPX can induce P53 expression which consequently promotes the cell apoptosis in MCF-7. Therefore, DPCPX could be used as an anti-cancer agent (Tab. 1, Fig. 3, Ref. 5). Text in PDF www.elis.sk.

The CD4*A4 allele has a susceptibility association with the development of vitiligo in the Iranian population (OR = 1.68, 95% CI 1.18-2.42; P < 0.01, P(c) = 0.02). When we compared CD4*A4-containing genotypes in the case and control groups, even more significant positive association was identified (OR = 2.02, 95% CI 1.26-3.22; P < 0.01 and P(c) < 0.01). The CD4 gene polymorphism has a modest association with the development of vitiligo in Iranian patients.

The 32-base pair deletion on the C-C chemokine receptor 5 gene (CCR5-delta 32) is known as a protective allele against immune system disorders. We have studied this variation in Iranian multiple sclerosis (MS) patients and healthy controls. DNA samples were prepared from the whole blood of 254 patients with MS and 380 healthy controls. We amplified the fragment including the CCR5-delta 32 polymorphism and visualized the products in a documentation system after agarose gel electrophoresis. Data were analysed using one-way ANOVA and Fisher's exact tests with SPSS-v13 and STATA-v8 software. The delta 32 allele was more frequent in MS patients when compared with controls (OR = 2.3, P < 0.0001). Also, we found a significant difference in the frequency of the delta 32/delta 32 genotype among patients and controls (OR = 7.4, P < 0.001). The mean age at onset and progression index was not significantly different between patients with various genotypes. According to our study, the delta 32 allele of the CCR5 gene might be a predisposing factor for MS development in the Iranian population. However, there were no associations between this polymorphism and the clinical course of the disease in this study.

Many studies have shown an association of IDDM with polymorphisms in the HLA region on chromosome 6p21. Previously our case-control study in the Belgian population showed significant association between IDDM and certain HLA class II alleles, in particular Lys`, +, encoding DRB1 alleles. In the present study, 81 Danish multiplex IDDM families and 82 healthy Danish controls were examined for polymorphisms in the HLA-DRB genes and 54 of the 81 families for polymorphisms in HLA-B, -DQAl, -DQBl, -TNFA, and -TNFB genes.The results confirm our previous studies in the Belgian population and show that DRBLYSl"+`+ homozygotes have a relative risk (RR) of 103.5. Linkage between IDDM and DRB1 alleles that encode Lys7"+ was shown by affected sib pair analysis which showed strong linkage (p<1 x 10-6). By family based association studies, the DRB1LYS7l`was identified as the allele which increased susceptibility to develop IDDM most in the HLA region (haplotype relative risk = 8.38). Haplotype analysis confirmed the increased risk contributed by DRB1LYS7l + alleles and in addition showed that DRBL""'l-provides protection against IDDM even in the presence of DQB1sp57-.These results indicate that DRBLYS7l+ screening is a powerful test compared to full HLA typing to determine the risk for a random person to develop IDDM in the Danish population, with an even higher probability than shown previously for the Belgians. (JMed Genet 1996;33:899-905) Key words: insulin dependent diabetes mellitus; HLA; amino acid polymorphism; linkage.Insulin dependent diabetes mellitus (IDDM) is characterised by the immunologically mediated destruction of the insulin producing islet 13 cells resulting in an absolute requirement for exogenous insulin administration. The aetiology of IDDM is complex, involving both genetic and environmental factors. A series of genetic components involved in IDDM susceptibility have been implicated, with a major susceptibility locus encoded by the HLA class II genes within the major histocompatibility complex (MHC) on chromosome 6p21. l6 Also, family studies showed that IDDM affected sib pairs have a non-random distribution of shared HLA haplotypes.7-10 Association studies between HLA class II polymorphisms and IDDM showed that alleles at the DR locus and at the DQ locus contributed to susceptibility or protection against IDDM. In particular, alleles DRB 1 *0401, DQBl*0302, DqocEg52I, and DQpAspl7-associated positively, while DRB 1 * 1500, *070 1, Dq?Arg52-, and DQ13AsP57+ alleles provided 2 11-18 protection.Previously we were able to assign the highest susceptibility to the DR3 LYS7l I alleles in the Belgian population, while the DQ1ASPS7-allele had an additive effect to developing IDDM in DR3 LYS7l±/I subjects'9 (Lys7l + is encoded by DRB1*0301,2,3, *0401, *0409, *1303). Indeed 60.9% of IDDM patients carried at least one copy of DRB 1 Lys71+, compared to about 19% of the control population and, even more significantly, approximately 38.6% of the IDDM patients were homozygous for DRBLYS7l+ alleles compared to...