1.
Impact of Serum Calcium Levels on Alzheimer's Disease: A Mendelian Randomization Study.
He, Y, Zhang, H, Wang, T, Han, Z, Ni, QB, Wang, K, Wang, L, Zhang, Y, Hu, Y, Jin, S, et al
Journal of Alzheimer's disease : JAD. 2020;(2):713-724
Abstract
BACKGROUND Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk. OBJECTIVE To develop effective therapies, we should establish the causal link between serum calcium levels and AD. METHODS Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate. RESULTS IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude. CONCLUSION In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.
2.
Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies.
Qu, J, Yang, ZQ, Zhang, Y, Mao, CX, Wang, ZB, Mao, XY, Zhou, BT, Yin, JY, He, H, Long, HY, et al
Journal of the neurological sciences. 2015;(1-2):56-62
Abstract
OBJECTIVE ATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population. METHOD Six ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI-TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls. RESULTS Significant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR)=0.807 (0.68-0.960), p=0.021 and 0.4% vs. 3.2%, OR=0.121 (0.026-0.565), p=0.002, respectively). The frequency of the rs8107107 CT+CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR=0.327 (0.248-0.942), p=0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance. CONCLUSION Our findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies.