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 GPXI 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 GPXI (rs1050450) and GPX4 (rs713041) were detected by allelic discrimination assay using TaqMan (R) MGB probes on a real-time PCR system. GPXI TT homozygotes had lower long-term visual memory scores than CC/CT group (-0.28 +/- 1.03 vs. 0.13 +/- 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, GPXI 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 GPXI and GPX4 are significantly associated with episodic memory and AD in a South Brazilian population.