Alzheimer Disease: Gürvit H

Dursun E, Gezen-Ak D, Ertan T, Bilgiç B, Gürvit H, Emre M, Eker E, Engin F, Uysal O, Yilmazer S. · Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. · Dement Geriatr Cogn Disord. · Pubmed #19155622 No free full text.

Abstract: BACKGROUND/AIMS: The polymorphism (rs1800587) in the 5'-flanking regulatory region at -889 of the interleukin-1alpha gene has been shown to be associated with inflammatory diseases and Alzheimer's disease (AD). The aim of the current study is to determine whether there is an association between the promoter region polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of Turkish patients. METHODS: One hundred and four subjects with dementia of the Alzheimer type and 103 age-matched controls were genotyped according to the PCR with confronting two-pair primers method. RESULTS: Although the distribution of genotypes did not significantly differ (p = 0.107), the difference between allelic frequency was nearly significant according to a chi(2) test (p = 0.05) when the controls and patients were compared. CONCLUSION: Our results showed that there is no association between the -889 C/T transition on the interleukin-1alpha gene and late-onset AD in the Turkish population.

Dursun E, Gezen-Ak D, Eker E, Ertan T, Engin F, Hanagasi H, Gürvit H, Emre M, Yilmazer S. · Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. · J Geriatr Psychiatry Neurol. · Pubmed #19017784 No free full text.

Abstract: Presenilin-1 is known to contribute to the pathogenesis of Alzheimer's disease. The association of an intronic polymorphism (rs165932) of the presenilin-1 gene with late-onset Alzheimer's disease has been documented. However, contradicting results have been shown in different populations. The aim of the current study is to determine whether there is an association between the intronic polymorphism of the presenilin-1 gene and late-onset Alzheimer's disease in a cohort of Turkish patients. One hundred and seven participants with dementia of the Alzheimer type and 106 age-matched controls were genotyped according to BamH I restriction site in intron 8 of the presenilin-1 gene. The distribution of genotypes and alleles did not significantly differ according to chi-square test (P = .52, P = .32, respectively), when the control and patients were compared. Consequently, our results showed that the 1/1 genotype does not increase the risk of developing late-onset Alzheimer's disease in the Turkish population.

Parildar-Karpuzoğlu H, Doğru-Abbasoğlu S, Hanagasi HA, Karadağ B, Gürvit H, Emre M, Uysal M. · Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey. · Neurosci Lett. · Pubmed #18672023 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a poorly understood etiology. There is considerable evidence that oxidative stress occurs in AD and increased DNA damage has been found in brain tissues and leukocytes of AD patients. Base excision repair (BER) is the major pathway responsible for removing oxidative DNA damage. Polymorphisms in DNA-repair genes have been associated with the increased risk of several age-related disorders including various types of cancer and could also be related to the etiology of AD. We conducted a case-control study including 91 patients with AD and age- and sex-matched 93 control subjects to examine the role of single nucleotide polymorphisms of BER genes, hOGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC1 (Arg280His and Arg399Gln) as a risk factor for AD. The frequencies of the hOGG1-Ser326Cys, APE1-Asp148Glu and XRCC1-Arg280His and XRCC1-Arg399Gln variant alleles in our control group were 0.23, 0.31, 0.10 and 0.33, respectively. No significant association was observed between the variant alleles of hOGG1-Ser326Cys (OR=1.32, 95% CI=0.83-2.11), APE1-Asp148Glu (OR=1.08, 95% CI=0.70-1.68), XRCC1-Arg280His (OR=0.53, 95% CI=0.24-1.14) and XRCC1-Arg399Gln (OR=1.05, 95% CI=0.68-1.63) and AD. Our results suggest that the polymorphic variants of these BER genes are not independent risk factors for AD.

Gezen-Ak D, Dursun E, Ertan T, Hanağasi H, Gürvit H, Emre M, Eker E, Oztürk M, Engin F, Yilmazer S. · Istanbul University, Cerrahpasa Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey. · Tohoku J Exp Med. · Pubmed #17592215 links to  free full text

Abstract: Vitamin D(3) is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D(3) to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and late-onset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype (p = 0.008, chi(2) = 9.577, OR = 2.30). Thus, the "Aa" genotype may increase the risk of developing AD 2.3 times when compared with the "AA" genotype. On the other hand, the "AT" haplotype was significantly higher in controls (p = 0.006) indicating a protective role of the "AT" haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D.

Doğru-Abbasoğlu S, Aykaç-Toker G, Hanagasi HA, Gürvit H, Emre M, Uysal M. · Department of Biochemistry, Istanbul University, Capa 34093, Istanbul, Turkey. · Neurol Sci. · Pubmed #17385092 No free full text.

Abstract: Alzheimer's disease (AD) is defined pathologically by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically significant (OR=1.95, 95% CI 0.88-4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96-4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the development of AD.