DNA variants in CACNA1C modify Parkinson disease risk only when vitamin D level is deficient

Abstract

Objective:To evaluate the association between the genetic variants in CACNA1C, which encodes the α1 subunit of the L-type voltage-sensitive calcium channel (LVSCC) and Parkinson disease (PD) while accounting for interactions with vitamin D concentration.Methods:Two independent case-control data sets (478 cases and 431 controls; 482 cases and 412 controls) were used. Joint effects of single nucleotide polymorphisms (SNPs) and SNP-vitamin D interaction were analyzed by comparing models containing vitamin D deficiency, SNP genotypes, SNP-vitamin D interaction, and covariates to a restricted model with only vitamin D deficiency and covariates. Meta-analysis was used to combine the joint effects in the 2 data sets. Analysis was stratified by vitamin D deficiency to demonstrate the pattern of SNP-vitamin D interaction.Results:Vitamin D deficiency was associated with PD in both data sets (odds ratio [OR] = 1.9–2.7, p ≤ 0.009). SNP rs34621387 demonstrated a significant joint effect (meta-analysis, p = 7.5 × 10−5; Bonferroni corrected, p = 0.02). The G allele at rs34621387 is associated with PD in vitamin D-deficient individuals in both data sets (OR = 2.0–2.1, confidence interval = 1.3–3.5, p = 0.002) but is not associated with PD in vitamin D–nondeficient individuals (p > 0.8 in both data sets).Conclusions:Previous studies suggest that vitamin D deficiency is associated with PD and sustained opening of LVSCC contributes to the selective vulnerability of dopaminergic neurons in PD. Our data demonstrate that the association between genetic variations in CACNA1C and PD depends on vitamin D deficiency, providing one potential mechanism underlying the association between vitamin D deficiency and PD.

Brain changes in neuroimaging of adult patients with vitamin D deficiency: systematic review protocol

“…In addition, calcitriol is also involved in the release of brain neurotransmitters and neurotrophic factors, 1 2 highlighting the anti-inflammatory mechanism of vitamin D reducing oxidative stress and release of inflammatory cytokines, attenuating or suppressing the autoimmune response. [3][4][5][6] Vitamin D deficiency is related to several pathologies of cerebral involvement, such as depression, 7 8 all types of dementia, Alzheimer, [9][10][11] Parkinson's disease [12][13][14] with systematic review and meta-analysis, from 2017 demonstrating that vitamin D deficiency contributes to dementia, 15 multiple sclerosis, 5 16 17 cerebral small vessel disease 18 it being an independent risk factor for cerebrovascular accident (CVA), 19 20 with vitamin D having a potential anti-inflammatory role in individuals diagnosed with CVA. 6 Among the cognitive symptoms most commonly related to vitamin D deficiency, cognitive decline and executive dysfunction stand out.…”

“…Vitamin D deficiency is related to several pathologies of cerebral involvement, such as depression,7 8 all types of dementia, Alzheimer,9–11 Parkinson’s disease12–14 with systematic review and meta-analysis, from 2017 demonstrating that vitamin D deficiency contributes to dementia,15 multiple sclerosis,5 16 17 cerebral small vessel disease18 it being an independent risk factor for cerebrovascular accident (CVA),19 20 with vitamin D having a potential anti-inflammatory role in individuals diagnosed with CVA 6…”

Sporadic Parkinson’s Disease Potential Risk Loci Identified in Han Ancestry of Chinese Mainland

“…Although genetic and environmental factors currently have been shown to lead to sPD, the etiology of sPD remains elusive ( Fahn, 2003 ). On the past unremitting effort, researchers have shed light on the relationship between some candidate genetic factors and sPD in different populations ( von Otter et al, 2014 ; Rozenkrantz et al, 2016 ; Soldner et al, 2016 ; Wang et al, 2016 ; Yang et al, 2016 ). These genetic factors included SNPs, rearrangements, and insertion/deletion polymorphisms; however, very few studies have been evaluated in Chinese populations, especially in the Han ancestry of Chinese mainland (HACM).…”

Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation

“…The role of the Ca v 1.2 isoform of L-type Ca 2+ channels (LTCCs) is well known in hippocampal-mediated long-term memory and related behaviors [1][2][3][4][5].The clinical relevance of this relationship is bolstered by the fact thatCACNA1 C, the gene that encodesCa v 1.2, is a prominent risk gene for a wide array of neuropsychiatric [2,3,6,7]andneurodegenerative [8][9][10][11]disorders that manifest with cognitive impairment.…”