Biomedical subjects

Metin Bagli

Publications and source records attributed to Metin Bagli.

3 recordsLinked to original sources

PubMed2003

Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study.

Interleukin-6 (IL-6) is a multifunctional cytokine involved in the pathogenesis of Alzheimer's disease (AD). The effects of IL-6 are mediated through a specific receptor complex made up of a ligand binding glycoprotein (gp80 or IL-6R) and a signal transducing glycoprotein (gp130). Conflicting results have been reported concerning altered IL-6 or soluble IL-6R (sIL-6R) levels in serum and CSF in AD. This study investigated whether genetic heterogeneity determines the magnitude of the difference in IL-6 and sIL-6R levels in AD. Fifty-eight AD patients and 25 control subjects were included. Plasma and CSF IL-6 and sIL-6R levels were measured and the IL-6 variable number of number repeats ( IL-6vntr) and IL-6 promoter ( IL-6prom) genotypes were determined. sIL-6R levels in plasma and CSF were higher in AD patients than in control subjects. This elevation was striking among non-carriers of the IL-6vntr*C allele and among subjects homozygous for the IL-6prom*C allele whereas no difference in plasma and CSF sIL-6R levels was observed among carriers of the IL-6vntr*C allele and among subjects with the IL-6prom*CG and IL-6prom*GG genotypes. We conclude that plasma and CSF levels of sIL-6R are significantly increased in AD patients and that the magnitude of increase is determined by the IL-6 genotype.

Aged↗

PubMed2002

Cerebrospinal fluid levels of beta-amyloid(42) in patients with Alzheimer's disease are related to the exon 2 polymorphism of the cathepsin D gene.

The intracellular aspartyl protease cathepsin D (catD) is involved in such Alzheimer's disease (AD)-related processes as the activation of the endosomal/lysosomal system and the cleavage of the amyloid precursor protein into amyloidogenic components, which may initiate neurodegeneration. A non-synonymous polymorphism (exon 2, C to T exchange leading to ala-->val substitution) of the gene encoding catD (CTSD) was previously associated with AD, in that the T allele increased the risk for AD. To investigate whether the T allele is associated with disease-related traits, we measured the concentration of the amyloid beta-peptide 1-42 (Abeta(42)) and 1-40 (Abeta(40)) in patients and control subjects. The T allele of the CTSD genotype was associated with a 50% decrease in Abeta(42) levels in the cerebrospinal fluid. Thus, we demonstrate a significant impact of the CTSD genotype on Abeta(42) levels in the cerebrospinal fluid of AD patients and underpin the importance of the validation of susceptibility genes by examining their potential pathophysiological relevance.

Aged↗

PubMed2002

Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.

Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD.

Adult↗