Review published in Advances in Nutrition finds variations in the vitamin D receptor gene associated with mild cognitive impairment and Alzheimer’s disease
The 2019 World Alzheimer‘s Disease Report notes that some 50 million people worldwide suffer from dementia, a figure that is expected to reach 152 million by 2050. Despite extensive studies, researchers still don’t know the exact root causes of dementia and how it evolves. It has, however, been hypothesized that certain genes may play a key role and that early identification of genetic risk factors may contribute to the prevention and treatment of dementia.
In particular, researchers believe that genetic variations, also known as gene polymorphisms, in the vitamin D receptor gene may play a key role in the onset and development of mild cognitive impairment and Alzheimer’s disease. The vitamin D receptor gene provides the instructions for making a protein known as vitamin D receptor, which, in turn, enables the body to respond to and make use of vitamin D.
Epidemiologic investigations have shown that low serum vitamin D concentrations increase the risk of cognitive decline. Moreover, older adults with vitamin D deficiency have a higher risk of developing Alzheimer’s disease. Because vitamin D deficiency has been reported to be associated with an increased risk of dementia, researchers have also suggested that variations in the vitamin D receptor gene may contribute to cognitive impairment. Study results linking vitamin D receptor gene polymorphisms to dementia to date, however, have been contradictory and uncertain, in part due to small sample sizes.
In response to this uncertainty, Nanyang Liu et al. conducted a meta-analysis “based on a larger sample size to clarify the contribution of vitamin D receptor gene polymorphisms to mild cognitive impairment and Alzheimer’s disease susceptibility.” The results of their review, “Vitamin D Receptor Gene Polymorphisms and Risk of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis,” were published in Advances in Nutrition, the international review journal of the American Society for Nutrition.
In order to conduct their meta-analysis, the authors performed an extensive search of the scientific literature for relevant studies published in either English or Chinese, eventually leading them to ten studies that met their criteria. Next, the quality of each study was assessed and statistical analysis was performed to judge the strength of the relations between various vitamin D gene polymorphisms and the risk of mild cognitive impairment and Alzheimer’s disease.
The results of the meta-analysis indicate that the vitamin D receptor polymorphisms ApaI and BsmI may be associated with the risk of developing mild cognitive impairment. In addition, the authors found that the TaqI polymorphism may be associated with the risk of Alzheimer’s disease. The authors did stress that the link between the vitamin D receptor gene and cognition was complex, noting that “the expression and effect of vitamin D receptor are determined by not only genetics but also race and environment and involve complex interactions that can change the connection with disease.”
“Considering the sample size, inclusion criteria, and characteristics of patients and controls,” the authors believe, “our results may provide the strongest evidence to date.” They did, however, acknowledge that their findings did have limitations, noting that “further studies with larger sample sizes are essential to reach clear conclusions.” These future research studies may, in turn, lead to the development of strategies to prevent or delay the onset of dementia as well as strategies to help slow, and possibly reverse, the progression of the disease.
Nanyang Liu, Tingting Zhang, Lina Ma, Wei Wei, Zehui Li, Xuefan Jiang, Jiahui Sun, Hui Pei, Hao Li, Vitamin D Receptor Gene Polymorphisms and Risk of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis, Advances in Nutrition, 2021;, nmab074, https://doi.org/10.1093/advances/nmab074.
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