VDR and CYP24A1 expression analysis in Iranian relapsing-remitting multiple sclerosis patients

Objective: Multiple sclerosis [MS] is a common disease of the central nervous system. This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor

Materials and Methods: In this case-control study, the expression of genes encoding vitamin D receptor [VDR] and CYP24A1 in relapsing-remitting MS [RR-MS] patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients [HLA-DRB1*15-negative and responders to interferon-beta with a normal vitamin D level] and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction

Results: The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group [P=0.04]. On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expanded disability status scale of Kurtzke [EDSS] and the expression level of either CYP24A1 or VDR. In addition, the expression level of CYP24A1 or VDR was not correlated with the duration of the disease

Conclusion: Up-regulation of VDR is likely to happen in RR-MS patients in the Iranian population. We did not observe a gene expression-phenotype correlation for CYP24A1 which may be due to limited statistical power as a result of the small sample size. Although the individuals taking part in this study had normal levels of vitamin D, the increase in VDR expression levels may perhaps be a response to a defect in vitamin D processing. Another possibility is that despite an increase in VDR expression level, factors such as micro-RNAs may result in their deactivation while an increase in VDR expression level can be seen as a compensatory response. Of course, further studies are required to identify the mechanism of action of vitamin D by analyzing genes involved in its signaling pathway, particularly VDR and CYP24A1

ANRIL genetic variants in Iranian breast cancer patients

Objective: The genetic variants of the long non-coding RNA ANRIL [an antisense non-coding RNA in the INK4 locus] as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients

Materials and Methods: In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms [SNPs] in 122 breast cancer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction [T-ARMS-PCR]

Results: The TT genotype at rs1333045 was significantly over-represented among patients [P=0.038] but did not remain significant after multiple-testing correction. In addition, among all observed haplotypes [with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278], four haplotypes were shown to be associated with breast cancer risk. However, after multiple testing corrections, TCGA was the only haplotype which remained significant

Conclusion: These results suggest that breast cancer risk is significantly associated with ANRIL variants. Future work analyzing the expression of different associated ANRIL haplotypes would further shed light on the role of ANRIL in this disease

Association analysis of DISC1 gene polymorphisms with Attention-Deficit Hyperactivity Disorder in Iranian population

Attention deficit hyperactivity disorder [ADHD] is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. In this research work, for the first time, we investigated the association of three SNPs [rs11122330, rs6675281 and rs11122319] in theD/5C7 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. [P value = 0.008, OR= 1.5837, 95% Cl= 1.1012 to 2.2776], Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world

The infl uence of -330 IL-2 gene polymorphism on relapsing remitting and secondary progressive multiple sclerosis in Iranian patients

Multiple sclerosis (MS) is a chronic infl ammatory demyelinating disease of the central nervous system. Interleukin-2 (IL-2) is identifi ed as the crucial and main immunoregulatory cytokines. Previously, we showed signifi cant association between -330 T/T IL-2 genotype and relapsing remitting MS among Iranian population. In this study we investigated 100 relapsing remitting, 30 secondary progressive MS and 125 healthy controls to compare the relapsing remitting and secondary progressive course MS in association to -330 IL-2 polymorphism. Our results showed that the -330 T/T IL-2 genotype was signifi cantly more frequent in relapsing remitting and secondary progressive MS than controls. The signifi cant increased frequency of -330 T/T IL-2 genotype in secondary progressive than relapsing remitting MS, imply -330 T/T IL-2 genotype can cause higher susceptibility to secondary progressive MS than relapsing remitting.

Investigation the role of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients

Type 1 diabetes mellitus [T1D] is an autoimmune and multifactorial disorder. Subsequent analysis on human leukocyte antigen [HLA] region shows that HLA-DRB1 and -DQB1 genes have the strongest association with T1D. In this study, for the first time, we investigated the influence of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients in order to determine gender dependent HLA heterogeneity in Iranian T1D patients. In this case control study, the HLA-DRB1 and -DQB1 typing were performed on 105 Iranian T1D patients and 100 healthy controls. The data were evaluated by using Fisher exact test. Our results indicate that DRB1*04:01, DQB1*03:02 alleles and DRB1*04:01-DQB1*03:02 haplotype were significantly more frequent in male T1D patients than females. Also, DRB1*03:01, DRB1*15:01, DQB1*06:01 alleles, DQB1*03:01/05:01 genotype, DRB1*03:01-DQB1*02:01 and DRB1*15:01-DQB1*06:01 haplotypes were significantly higher in female T1D group than males. Furthermore, our results showed that DRB1*04:01 and DQB1*03:02 alleles were significantly more frequent in male T1D patients 1-5 years old at onset than females with similar condition. The DRB1*03:01 allele and DRB1*03:01-DQB1*02:01 haplotype were significantly higher in female T1D patients 6-10 years old at onset than males with similar condition. The DRB1*15:01 allele and DRB1*15:01-DQB1*06:01 haplotype were significantly more frequent in female T1D patients 16-20 years old at onset than males with similar condition. Our findings suggest that gender has a significant influence on the distribution of HLA-DR and -DQ alleles, genotypes and haplotypes. Also, distribution of the HLA-DRB1 and -DQB1 alleles, genotypes and haplotypes vary based on the gender of T1D patients in different age at onset

association of -475 and -631 interleukin-2 gene polymorphism with multiple sclerosis in Iranian patients

Multiple sclerosis [MS] is a chronic autoimmune disease due to demyelination of the central nervous system. It is believed that cytokines are involved in the pathogenesis of MS. The interleukin-2 [IL2] gene is powerful functional candidate that is involved in immune regulation and operation. In this study, for the first time, we investigated the effect of -475 A/T and -631 G/A IL2 polymorphisms on MS disease in Iranian patients. In this case-control study, 100 MS patients [mean age: 32.95 +/- 6.51 years, age range: 20-42 years] selected according to McDonald criteria, and 100 ethnically, sex and age matched healthy controls [mean age: 29 +/- 7.8 years, age range: 20-52 years] with no personal or family history of autoimmune diseases were studied. The restriction fragment length polymorphism-polymerase chain reaction [RFLP-PCR] method was applied to define different alleles and genotypes of IL2 promoter single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals. chi [2] was calculated and Fisher's exact test was applied to analyze the obtained data. The value of p <0.05 was considered significantly. Evaluation of the -475 IL2 revealed that T allele and A/T genotype are present in 2% and 4% of MS patients, respectively, whereas T allele was absent in control samples. The comparison between alleles and genotypes in MS patients and healthy controls was not significant [p=0.1]. For the -631 position, 1% and 2% of MS patients carried A allele and A/G heterozygote genotypes, respectively. All control samples had G allele and G/G genotype. The differences between patients and controls were not significant [p=0.4]. Moreover, our results showed a very low frequency of T at -475 and A at -631 IL2 position in each of the two groups. Both -475 and -631 IL2 polymorphisms were higher in MS patients as compared to controls, but the frequency differences were not significant. Based on these data, it is suggested that the -475 and -631 IL2 polymorphisms as functional promoter position may be involved in IL2 expression and regulation. To find out the exact effect of the mentioned SNPs on susceptibility to MS, study on a larger sample size is suggested

[ influence of HLA-DRB1,-DQB1 genes on age at onset of type 1 diabetes in Iranian T1D patients]

Survey of the influence of HLA-DRB1,-DQB1 alleles, genotypes and haplotypes on age at onset of type 1 diabetes [T1D] in an Iranian population 105 Iranian T1D patients of different ethnic group and 100 ethnically, age and sex matched individuals were selected from Tehran's hospitals and HLA-DRB,-DQB typing was performed. According to the age at onset of T1D, the patients were divided into 4 groups [1-5, 6-10, 11-15, 16-20 years]. The frequency of susceptible and protective alleles, genotypes and haplotypes was calculated in each group. The data were evaluated by using fisher's exact test. Odds Ratio or relative Risk was measured for all samples. The results illustrated that the frequency of the HLA-DRB1*0401 allele decreased with increasing age, whereas the frequency of the HLA-DQB1*0201 allele increased with increasing age. The HLA-DRB1*0301 and HLA-DQB1*0302 alleles demonstrated the highest frequency in the 6-11 and 1-5 years age at onset group, respectively. HLA-DRB1*0401-DQB1*0302 haplotype had the most frequency among the 1-5 years age at onset group [p: 2x10-7, OR: 69.919] and the frequency of HLA-DRB1*0301-DQB1*0201 haplotype was the highest in the 6-11 years age at onset group among others [p: 2x10-6, OR: 6.243]. The current study indicated that HLA-DRB1,-DQB1 alleles, genotypes and haplotypes are associated with age at onset of type1 Diabetes in Iranian T1D patients. The individuals carrying alleles that are associated with younger age at onset should take care under preventive treatment