[Glutathion-S-Transferase M1, T1 and P1 gene polymorphisms in autoimmune hepatitis]

Autoimmune hepatitis [AIH] is a chronic inflammatory liver disorder of unknown etiology. The search for gene polymorphisms has suggested that Glutathion-s-transferase [GST], enzymes that metabolize carcinogens, drug, and foreign compounds, may play a role in susceptibility to autoimmune liver disease and its severity. The objective of this study was to investigate for a relationship between the glutathion-s-transferase M1, T1 and P1 genotypes and type 1 autoimmune hepatitis. In a case-control study, we investigated glutathion S-transferase [GST] P1 Ile [105] Val, T1, and M1 polymorphisms in 64 type 1 AIH patients and 100 healthy controls that were selected consecutively. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex PCR procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. GSTM1 and GSTT1 null genotypes [deletions] were determined in 33[51.6%] and 15 [23.4%] patients with type 1 AIH, and 56 [56%] and 22[22%] controls, respectively. Comparison of patients and controls relative to GSTM1 and GSTT1 genotypes revealed no significant difference between them. Regarding GSTP1 genotypes, 25[39.1%] heterozygotes, 7 [10.9%] homozygotes in the case group and 38[38%] heterozygotes, 14[14%] homozygotes in the control group were observed. The allele frequency of GSTP1 [Val] was 30.4% and 33 % in patients and controls, respectively. There were no significant variation in GSTP1 frequencies between cases and controls. These results suggest that there is no association between GST M1, GSTT1 and GSTP1 gene polymorphisms and type 1 autoimmune hepatitis in Iran

[Association of the vitamin D receptor gene polymorphisms with inflammatory bowel disease in Iran]

Different genes such as vitamin D receptor [VDR] gene have some roles in IBD susceptibility. Some studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms [Apa I, Taq I, Bsm I, Fok I] with IBD in Iran. In this case-control designed study 100 UC, 50 CD patients and 150 sex and age matched healthy controls, hospital base, were selected. These patients were referred to [Taleghani Hospital] during a one year period [2004-2005]. Assessment of VDR gene polymorphisms was performed by PCR-RFLP method. Only the frequency of the Fok I polymorphism was significantly higher in UC and CD groups. The frequency of the polymorphic allele f was higher in UC and CD groups comparing with controls [p=0.019, OR=1.581 and p<0.001, OR=2.642, respectively]. The f/f genotype was significantly more frequent in UC and CD patients comparing with controls [p=0.010, OR=2.774 and p<0.001, OR = 5.947, respectively]. There were no significant differences between frequencies in patients and controls in other polymorphisms. There is a relation between Fok I polymorphism in VDR receptor gene and IBD in Iran but no association was observed with other 3 polymorphisms

Frequency and biochemical expression of hemochromatosis [HFE] gene mutations in 1029 blood donors in Iran

There are no data on the frequency and biochemical expression of the hemochromatosis associated mutations, C282Y and H63D, in Iranian adult population. This is the first study among Iranians that may advocate a screening program. We investigated the frequency of the C282Y/H63D HFE gene mutations in a group of 1029 randomly selected Iranian blood donors as well as transferrin saturation [TS], serum iron and serum ferritin levels. DNA extraction with salting-out method was performed on blood samples and the analysis of HFE gene mutations was performed by PCR amplification followed by digestion with RsaI and BclI restriction enzymes. The mean age of donors was 40 +/- 11 years and 92.7% were male. No homozygosity was detected for the C282Y mutation. Heterozygosity for the C282Y mutation was 0.2%, while homozygosity and heterozygosity for the H63D mutation were 1.6% and 19.6%, respectively. There was no compound heterozygote for the C282Y/H63D mutation. These data resulted in allele frequencies of 0.1% and 11.3% for C282Y and H63D mutations, respectively. Serum iron and TS were not influenced by the type of C282Y and H63D mutation. There was no difference in ferritin levels according to type of HFE mutations among blood donors. This study shows low allele frequency for C282Y and H63D mutations in Iran. These results also suggest that there is not any association between HFE gene mutations and iron, TS and ferritin level among Iranian population. The genetic screening for the HFE gene mutation in Iran is not recommended until the true prevalence of other mutations in all hemochromatosis genes could be established

CTLA 4 polymorphism at position 49 in exon 1 and susceptibility to type 1 autoimmune hepatitis

CTLA-4 expressed on activated T cells, binds to B7 molecules and functions as a negative regulator of T cell activation. In theory, reduced expression or function of CTLA-4 might augment autoimmunity. Recently an A-G polymorphism in exon 1 of the CTLA-4 gene was associated with predisposition to AIH type1 [AIH-1] and several other autoimmune diseases in white individuals in distinct populations. We investigated the frequency of this polymorphism in Iranian patients with AIH-1, using a case-control association analysis. Peripheral blood mononuclear cells' DNA were prepared from AIH patients [n=76] and healthy controls [n=185]. Determination of CTLA-4 genotypes was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The allele frequency for G allele was 25.6% and 24.3% in patients and healthy controls, respectively that shows no significant difference in subjects with AIH as compared to the healthy controls. Meanwhile, the frequencies of AA, AG and GG genotypes in patients and in healthy controls revealed no statistical difference in the distribution of CTLA-4 genotype in the studied groups. This study demonstrates that susceptibility to AIH in Iranian population is not influenced by exon 1 CTLA-4 gene polymorphisms at position 49. This polymorphism may either have a recent founder population or be associated with AIH only among the Caucasians