Correlation Between 25-hydroxy-Vitamin D and Parkinson's Disease:A Case-Control study

Background: Previous cross-sectional studies have shown that Parkinson’s disease (PD) patients have lower serum 25- hydroxy vitamin D (25(OH)D) concentrations than controls. whether the research in other regions ndings are generalizable to China populations remains untested in other studies. In this case-control study we examined the Correlation between 25-hydroxy-vitamin D and Parkinson's disease. Methods:We establish an association between deciency of 25-hydroxy-vitamin D and PD in a case-control study of 100 PD patients and 100 control subjects free of neurologic disease in the First Aiated Hospital of Xinjiang Medical University. Results:Total 25-hydroxy-vitamin D levels, were decient in 21% of patients with PD compared with 4% of controls. In univariate analyses Plasma levels of 25-hydroxy-vitamin D were associated with PD(p<0.001), respectively. In multivariate analyses, Vitamin D deciency(25(OH)D <20 ng/mL) were signicant associated with PD (p=0.008,OR=17.13,95% CI, 2.082-141.075). Individuals with levels in the lowest quartile of 25(OH)D values had the highest prevalence of PD(p =0.026,OR=11.786,95%CI,1.342-103.51)compared with individuals with values in the highest quartile. Conclusions:Our study reveals an association between 25-hydroxy-vitamin D and PD.Patients with incident PD had signicantly lower serum 25(OH)D concentrations than age-matched controls, High-risk PD patients with vitamin D deciency who have not yet developed exercise impairment, these populations should undergo vitamin D measurement and vitamin D treatment as soon as possible.


Background
Parkinson's disease (PD) is a common neurodegenerative disorder that the incidence and disability continue to increase as the population ages [1].Although both genetic and environmental factors have been implicated, its etiological factors are mostly unknown [2]. Recently,among the many pathogenesis of Parkinson 's disease,people found a commonality {25-hydroxy-vitamin D [25 (OH) D]de ciency}, which suggests that there is a correlation between 25 (OH) D levels and Parkinson's.Evatt [3]et al retrospective cross-sectional cohort study found demonstrates a signi cantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD.Ding [4]et al study showed that vitamin D de ciency in 17.6% of cases (68/388) compared with 9.3% of controls (26/283; p = 0.002),Plasma levels of 25hydroxy-vitamin D3 were associated with the prevalence of PD in both univariate and multivariate analyses (P = 0.0034 P = 0.047).The Mini-Finland Health Survey, people in the lowest quartile at baseline had approximately three times the risk of developing PD compared with people in the highest quartile [5].
Sun-light exposure is the major source for vitamin D [6] .The production of vitamin D depends not only on the intensity of ultraviolet rays, but also on the duration of ultraviolet irradiation [7] and there are differences between different regions and races.Wang [8]et alCase-control studies found that a signi cant positive correlation between serum 25(OH)D and sunlight exposure.lower levels of serum 25(OH)D and sunlight exposure are signi cantly associated with an increased risk for PD.A few case-control studies in Finland ,Iran ,Japan and the United States have reported lower 25(OH)D levels in PD patients compared with age-matched controls [9][10][11].
Affected by the region, the annual sunshine hours in Xinjiang, China are 3200-3300, and the average annual sunshine hours under standard illumination are 5.08-6.3, which is higher than that in other regions of China [12]. whether the research in other regions ndings are generalizable to China populations remains untested in other studies. To address these limitations in previous investigations, in our study, we used immunoassay-based vitamin D measuring assays to investigate an association between de ciency of the 25(OH)D and PD in the First A liated Hospital of Xinjiang Medical University from January 2019 to December 2019.

Study Design and Population
In our study,we collected 100 with PD and 100 control subjects without neurologic disease nested in the First A liated Hospital of Xinjiang Medical University from January 2019 to December 2019.Inclusion criteria for PD cases were conforms to the new standard for clinical diagnosis of Parkinson's disease of the International Dyskinesia Association [13].Exclusion criteria for PD cases were diagnosis of endocrine system diseases such as hyperparathyroidism and other diseases of abnormal calcium and phosphorus metabolism,fractures or bone tumors recently (≤ 6 months);known active ulcer, or active colitis.Inclusion criteria for healthy controls were no current diagnosis or history of a neurologic disease. Exclusion criteria for controls were the same as for cases. Controls were comparable to the PD cases in that they were drawn from the same source population and could be identi ed as cases, if they had disease.
This study protocol was approved by the institutional review boards of Ethics Committee of First A liated Hospital of Xinjiang Medical University. This study is a retrospective study, we don't need to obtain informed consent from eligible patients.

Clinical and Demographic Characteristics Collection
Baseline characteristics of cases and controls were examined (Table 1), including factors known to affect vitamin D status such as age, sex, race, smoking status,uric acid,blood calcium,fasting blood glucose,glycated hemoglobin.   Several studies have reported an association of PD with lower plasma 25(OH)D concentrations [17][18][19]. Ding et al [4]study shows that there was vitamin D de ciency in 17.6% of cases (68/388) compared with 9.3% of controls (26/283; p = 0.002). After adjusting for for age, sex, race, and vitamin D supplementation,de ciency of total 25(OH)D remained enriched in PD with p = 0.03. Wang et al [20]study shows that Vitamin D de ciency (total 25 (OH) D < 20 ng / mL) was signi cantly correlated with PD (P < 0.0001).The lowest quartile of 25(OH)D values had the highest prevalence of PD with an OR = 2.66, P < 0.0001 (95%% CI, 1.746-4.03) compared with individuals with values in the highest quartile.Our study also draws results consistent with the above studies,in our case-control study, cases are 11.786 times as likely as controls to be in the lowest quartile compared with the highest quartile.
Suzuki et al [21] conducted a randomized, double-blind, placebo-controlled vitamin D intervention trial,the results showed that vitamin D signi cantly inhibited the deterioration of the Hoehn-Yahr staging score of PD patients compared with placebo. [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. It is suggested that vitamin D has a delaying effect on the severity of disease in PD patients, and does not cause adverse reactions such as hypercalcemia.
In our study, it was veri ed that there is a certain correlation between VD and H-Y classi cation.Especially for patients who does not yet exist with motor dysfunction (HY grade < 3),There was a signi cant negative correlation between serum VD concentration and H-Y grade.Therefore, it can be inferred that VD can be used as an index to predict the severity of PD before PD sports injury.The lower the serum VD concentration in PD patients, the more likely to be exercise impairment.
Sleemana et al [22]study result showed that mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1 ± 21.7 vs. 52.2 ± 22.1 nmol/L, p < 0.05) and 18 months (44.2 ± 23.6 vs. 55.7 ± 28.8 nmol/L, p < 0.05). There was a small but signi cant association between vitamin D status at baseline and disease motor severity at 36 months.
Our study is consistent with previous study results, and there is a certain correlation between VD and disease course.Especially for patients with a long course of disease (course > 6 months), the course of disease is signi cantly negatively correlated with serum VD concentration. With the extension of the course of disease, the value of VD in the serum of PD patients will decrease accordingly.
A prospective study [23]showed that there are no support to the hypothesis that vitamin D may reduce the risk of PD.In other words, supplementing VD before the disease cannot reduce the incidence of PD. Meamar [10] et al study con rmed that supplementing VD during PD cannot delay the development of the disease.Previous reports indicate that there is a signi cant difference in the biochemical levels of bone metabolism between PD cases and the control group, this may be due to the impact of PD, not the direct role of PD pathogenesis.
Scherzer [24] et al study pointed out that vitamin D has been produced in rats to improve the toxicity induced by 6-hydroxydopamine.Our study also shows that there is a certain correlation between VD and H-Y classi cation, but the correlation is not signi cant (R 2 = 0.4). Studies have shown that there is a certain polymorphism of VDR in the central nervous system, and this polymorphism affects the impact of VD on its downstream response. However, it is not su cient to explain the problem only by genetic polymorphism, so further research is needed to con rm it.
There are several limitations in our study.First,our study was conducted on patients and controls in the First A liated Hospital of Xinjiang Medical University, not the general Chinese population. The population and ethnic composition of this region and the differences in life are large. It is necessary to evaluate the population lacking vitamin D in other regions of China.Second,because of the relationship between detection methods, our study failed to detect the association between vitamin D from different sources and PD, only to show the correlation between serum VD concentration and PD disease progression, which needs further exploration in the next study.Three,our study is a case-control study and lacks longitudinal clinical evaluation, including multiple vitamin D measurements that fail to assess the relationship between vitamin D status (and its changes over time) and disease progression. In order to provide valuable information, the time window is essential for adequate exposure of vitamin D to prevent or delay the onset of PD. It is necessary to study the longitudinal cohort at different periods to provide valuable information.

Conclusion
In our study,the nding of a high incidence of vitamin D de ciency in the PD.High-risk PD patients with vitamin D de ciency who have not yet developed exercise impairment, these should undergo vitamin D measurement and vitamin D treatment as soon as possible.Particularly in elderly patients, the de ciency is closely related to the content of vitamin D.