Biomedical subjects

M Fedetz

Publications and source records attributed to M Fedetz.

5 recordsLinked to original sources

PubMed2006

The 1858T PTPN22 gene variant contributes to a genetic risk of type 1 diabetes in a Ukrainian population.

The 1858T variant of the protein tyrosine phosphatase gene, PTPN22, is associated with an increased risk of several autoimmune diseases. The aim of this study has been to investigate the possible association of 1858C-->T PTPN22 polymorphism and type 1 diabetes (T1D) in Caucasians from Ukraine. Overall, the distribution of 1858 PTPN22 genotypes differed significantly between the T1D patient group (n = 296) and the control group (n = 242) (P = 0.0036). When both groups were classified according to sex, the TT genotype and T allele showed a statistically significant higher frequency in T1D female patients (5.9 and 22.8%, respectively) in comparison with the female controls (0 and 11.9%) (P = 0.008 for both analyses). The patients with the TT genotype were significantly younger at the onset of T1D compared with those with genotypes TC and CC (P = 0.035 and 0.019, respectively). In our Ukrainian Caucasian cohort, we confirmed the association between T1D and the PTPN22,1858T allele.

Adolescent↗

PubMed2006

OAS1 gene haplotype confers susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is associated with genetic susceptibility and unknown environmental triggers, possible viral infections, but the specific etiological mechanism that subsequently develops into an inflammatory/autoimmune cascade of events is poorly understood. Recently, genetic variants of 2',5'- oligoadenylate synthetase 1 (OAS1) gene, a critical enzyme involved in innate antivirus response, have been associated with differential enzyme activity and type 1 diabetes in both case-control and family studies. We hypothesized that polymorphisms in the OAS1 gene could influence the susceptibility to MS. To test this hypothesis, we conducted a case-control study of 333 patients with MS and 424 healthy controls and genotyped two OAS1 single nucleotide polymorphisms (SNPs) by restriction fragment length polymorphism method: rs 10774671, A/G SNP altering the splicing site at the seventh exon, and rs 3741981, a nonsynonymous (Ser162Gly) A/G SNP in the third exon. Haplotype but not single-marker analysis revealed an association of the haplotype created by the G allele at rs 10774671 and the A allele at rs 3741981 with the susceptibility to MS (P value = 8.8 x 10(-5)). Subjects carrying this haplotype had an increased risk of MS comparing with those not carrying it (odds ratio = 4.7, 95% confidence interval 2.1-10.9). Our findings indicate that the OAS1 gene polymorphisms may confer susceptibility to MS or serve as markers of functional variants and suggest that OAS1 activity is involved in the etiology of the disease. Future studies in a larger sample and association analysis with functional variants will clarify the role of the OAS1 gene in the susceptibility to MS.

2',5'-Oligoadenylate Synthetase↗

PubMed2002

Analysis of -631 and -475 interleukin-2 promoter single nucleotide polymorphisms in multiple sclerosis.

We have analysed the interleukin-2 (IL-2) promoter single nucleotide polymorphisms -475 A/T and -631 G/A, relative to the initiation codon, in patients with multiple sclerosis (MS) and in healthy controls. Both groups showed a very low frequency of T at -475 and A at -631. Our results suggest that these polymorphisms do not contribute to MS susceptibility.

Genetic Predisposition to Disease↗

PubMed2001

The -174/-597 promoter polymorphisms in the interleukin-6 gene are not associated with susceptibility to multiple sclerosis.

Interleukin-6 (IL-6) has been implicated in the etiology of experimental autoimmune encephalomyelitis (EAE) in transgenic animals and contributes to neuropathology in humans. A single nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter (IL-6pr) appears to influence IL-6 expression. Complete linkage disequilibrium was observed between the -174 and the -597 alleles. The aim of this study was to investigate the possible influence of -174/-597 IL-6pr polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping of the -597 variant was performed by an RFLP method in 131 MS patients [88 relapsing-remitting (RR-MS), 43 secondary progressive (SP-MS)] and 157 healthy subjects. No differences were found between MS patients and controls with respect to the distribution of -597 IL-6pr genotypes. Neither was found when genotypes were analyzed according to the clinical course of the disease (RR-MS or SP-MS). Future studies focusing on complex transcriptional interactions between the IL-6pr and 3' flanking region polymorphic sites will be necessary to determine the IL-6 haplotype influence on susceptibility to MS.

Adult↗

PubMed2001

Allelic expression and interleukin-2 polymorphisms in multiple sclerosis.

We have investigated the association of two single nucleotide polymorphisms (SNPs) at positions -384 and 114 in the human interleukin-2 (hIL-2) with multiple sclerosis (MS). For two of the -384 genotypes (G/T, T/T), we observed an association with the susceptibility to secondary progressive (SP) course of MS (P=0.005 and P=0.013, respectively). Expression level differences of the IL-2 alleles (between one- and three-fold) were not attributable to the -384 promoter polymorphism. These data indicate for the first time the relevance of the il-2 gene locus in human MS and its possible involvement in other autoimmune diseases.

Age of Onset↗