Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study

Abstract

BackgroundLow circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology.MethodsTen thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria.ResultsLower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels.ConclusionsWe found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.

Serum vitamin D levels in relation to abdominal obesity: A systematic review and dose–response meta‐analysis of epidemiologic studies

“…Seven researches separately investigated the relationship between vitamin D levels and abdominal obesity in men and women, 10 included studies were done in women and 24 others were conducted in both genders. Although most studies considered at least two levels of serum vitamin D and reported ORs for the highest versus lowest levels (or vice versa) of this exposure ( n = 36), five other investigations reported ORs for serum vitamin D as a continuous variable, 16,52,53,61,65 so the latter reports were included only in linear dose–response analysis. Some included studies that considered sufficient serum vitamin D levels as the reference category to report ORs or RRs, while others defined deficient serum vitamin D levels as the reference.…”

“…14,16 The included cross-sectional and cohort studies have included a total of 269,258 and 6,278 participants, respectively. Nine of cross-sectional studies were carried out in South Korea, 9,12,17,[40][41][42][43][44][45] four in United States, 10,[46][47][48] four in Iran, 19,[49][50][51] three in China, 8,52,53 two studies in the Netherlands, 11,54 Russia, 13,55 Spain 56,57 and the remaining in Iceland, 56 Ireland, 56 Australia 58 Brazil, 21 California, 59 India, 20 Japan, 60 Portugal, 61 Jordan, 62 Malaysia, 63 Mexico, 22 Norway, 14 Romania, 64 Thailand, 15 Saudi Arabia 18 and United Arab Emirates. 65 Two cohort studies were also done in Australia 16 and Norway.…”

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020

“…Mendelian randomisation studies, in which genetically predicted, rather than measured, 25(OH)D concentration is used to test a link with health outcomes can overcome some of the biases inherent in observational studies. Several recently published Mendelian randomisation studies have failed to identify links between vitamin D and cardiovascular/metabolic diseases, depression, non-vertebral fracture, all-cause mortality [ 97 , 98 ], or cognitive and psychiatric traits [ 99 ].…”

Impact of the Glycemic Control and Duration of Type 2 Diabetes on Vitamin D Level and Cardiovascular Disease Risk

“…Experimental studies found that (1,25(OH) 2 D 3 ) stimulated pancreatic β-cell to secrete insulin [14]. Another proposed mechanism regarding the role of vitamin D in T2D is that since vitamin D deficiency causes an increase in inflammatory markers, insulin resistance may develop [15]. However, other intervention studies found no improvement in glycemic control with vitamin D supplementation [9,16].…”