Association of GPX1 and GPX4 polymorphisms with episodic memory and Alzheimer's disease.

It is well established that healthy aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) are associated with substantial declines in episodic memory. However, there is still debate about the roles of GPX1 and GPX4 polymorphisms. The aim of this study was to investigate the association of rs1050450 and rs713041 polymorphisms with memory. This research was composed of a cross-sectional study (334 subjects) and a case-control study (108 healthy controls and 103 with AD-NINCDS/ARDA, DSM-IV-TR criteria). For the association of the genetic polymorphisms with memory or cognitive loss, the phenotypes were analyzed as follows: 1) each memory as a quantitative trait; 2) presence of deficit on a specific memory; 3) presence of MCI; 4) presence of AD. To assess verbal learning and the ability to store new information, we used the Rey Verbal Learning Test. Scores were recorded as a function of age as in the WMS-R testing battery. DNA was obtained from whole blood, and genotypes for GPX1 (rs1050450) and GPX4 (rs713041) were detected by allelic discrimination assay using TaqMan® MGB probes on a real-time PCR system. GPX1 TT homozygotes had lower long-term visual memory scores than CC/CT group (-0.28 ±â€¯1.03 vs. 0.13 ±â€¯1.03, respectively, p = 0.017). For the GPX4 rs713041, the frequency of the TT genotype was higher in the group with normal scores than in the group with long-term visual memory deficits (p = 0.025). In a multivariate logistic regression, GPX1 CC homozygotes had a 2.85 higher chance of developing AD (OR = 2.85, CI95% = 1.04-7.78, p = 0.041) in comparison to the reference genotype. No significant differences were observed regarding the MCI group between genetic variants. This study is one of the first to show that polymorphisms in GPX1 and GPX4 are significantly associated with episodic memory and AD in a South Brazilian population.

Association between DNA methyltransferase gene polymorphism and Parkinson's disease.

Parkinson's disease (PD) is a common and complex neurodegenerative disorder, the second most prevalent, only behind Alzheimer's disease. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, that is carried out by enzymes, such as DNMT1 and DNMT3B. This present study targeted to investigate the association among DNMT1 and DNMT3B polymorphisms with PD. Five hundred and twenty-two participants (214 PD patients following UK Brain Bank criteria and 308 healthy individuals) were evaluated. DNA was obtained from whole blood and genotypes were detected by an allelic discrimination assay using TaqMan® MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560 and rs759920 (DNMT1) and rs2424913, rs998382 and rs2424932 (DNMT3B). Was found association between DNMT3B rs2424913 in T allele carriers with PD. The presence of the T allele was associated with PD (OR=1.80, 95% CI 1.16-2.81, p=0.009). No significant difference was observed for others DNMT3B SNPs. Also, no association between PD and the control group were observed for DNMT1 polymorphisms. This is the first study addressing an association between DNMT3B polymorphism and PD. The polymorphism may play a role in the pathogenesis of PD.

SLC30A3 and SEP15 gene polymorphisms influence the serum concentrations of zinc and selenium in mature adults.

Because of their numerous roles in several biological processes, zinc and selenium are the most commonly studied micronutrients in the elderly. Therefore, we hypothesized that the polymorphisms in the genes that are responsible for the transport of zinc and selenium may have a genotype-dependent effect on the serum concentration of these micronutrients. The objective of this study was to determine the effects of solute carrier family 30 member 3 (SLC30A3) and 15-kd selenoprotein (SEP15) polymorphisms on zinc and selenium concentrations, respectively, in the serum. This cross-sectional study included 110 individuals who were aged 50 years or older. Serum micronutrient concentrations were determined by flame atomic absorption spectrophotometry (for zinc) and by atomic absorption spectrophotometry with a graphite furnace (for selenium). The single-nucleotide polymorphisms, rs73924411 and rs11126936 of the SLC30A3 gene and rs5859, rs5854, and rs561104 of the SEP15 gene, were examined by real-time polymerase chain reaction. Regarding rs11126936, the serum zinc concentration was lower in CC homozygotes (0.75 ± 0.31 mg/L) than in A carriers (0.89 ± 0.28 mg/L, P = .016). Concerning rs561104, the serum selenium concentration was higher in CC homozygotes (5.65 ± 1.11 µg/dL) compared with T carriers (4.88 ± 1.25 µg/dL, P = .044). Our results demonstrate the influence of SLC30A3 and SEP15 gene polymorphisms on the serum concentrations of zinc and selenium, respectively. The effects of these associations should be further investigated to help elucidate the modes of action of trace elements and to identify biomarkers, which could ultimately define the optimal intake of these micronutrients at the molecular level. More research must be performed before the roles of these polymorphisms in the serum concentrations of zinc and selenium can be fully understood.

The effects of interactions between selenium and zinc serum concentration and SEP15 and SLC30A3 gene polymorphisms on memory scores in a population of mature and elderly adults.

Memory deficits are common during aging, but little is known about the impact of environmental and genetic variables on memory. The genes SLC30A3 and SEP15 are, respectively, responsible for transporting zinc and selenium, micronutrients that are neuroprotective agents. The aim of this study was to investigate the effect of nutrigenetic interactions on the memory scores of volunteers more than 50 years old. For this cross-sectional study, 240 individuals were enrolled. Micronutrient dosage was determined using atomic absorption spectrophotometry. The SNPs rs5859, rs5854, and rs561104 in SEP15 and rs73924411 and rs11126936 in SLC30A3 were determined by real-time PCR. The evaluations of verbal and visual memory were performed using the Weschler Memory Scale-revised and the Rey's verbal learning test. A gene versus nutrient interaction was observed for SLC30A3 rs73924411 and zinc concentration. Carriers of the T allele had higher scores for short-term and long-term verbal memories than CC homozygotes only when zinc serum concentration was below the recommended level (p value for the interaction for short-term verbal memory = 0.011, p value for the interaction for long-term verbal memory = 0.039). For SEP15, C carriers of the rs5845 SNP allele had higher verbal learning memory scores than TT homozygotes (0.13 ± 1.13 vs. -1.10 ± 1.20, p = 0.034). Our results suggest the influence of genetic polymorphisms on memory score and identify gene versus nutrient interactions between zinc serum concentration and memory score.