Meta-Analysis of the Association Between the rs228570 Vitamin D Receptor Gene Polymorphism and Arterial Hypertension Risk

Abstract

The association between FokI polymorphism in the vitamin D receptor (VDR) gene and susceptibility to arterial hypertension (HT) is controversial. Thus, we evaluated the relation between FokI and HT according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE® (Medical Literature Analysis and Retrieval System Online)/PubMed, Scopus, and Cochrane Library CENTRAL databases. Data from case-control studies, including the number of participants, age, 25-hydroxyvitamin D concentrations, systolic and diastolic blood pressure values, FokI allele, and genotype frequency were extracted by 2 independent authors and OR was calculated with the 95% CI to assess the strength of the association between the FokI variant and odds of HT. In general and subgroup analyses, we used allelic (f compared with F), common (ff compared with FF + Ff), risk (ff + Ff compared with FF), and additive (ff compared with FF) models. Six case-control studies including 3140 cases and 3882 controls were reviewed in the meta-analysis. Global assessment revealed a correlation between FokI and reduced odds of HT in the additive/homozygote model (ff compared with FF; OR: 0.65; 95% CI: 0.45–0.94) and common/recessive model (ff compared with FF + Ff; OR: 0.75; 95% CI: 0.57–0.99). In Asian subjects, there was a significant reduction in the odds of HT in additive (ff compared with FF; OR: 0.84; 95% CI: 0.73–0.98) and risk models (ff + Ff compared with FF; OR: 0.87, 95% CI: 0.78–0.97), in particular, for Indians (South). In Africans, the statistically significant association occurred in the additive and common models. Allele f in the FokI polymorphism of the VDR gene was associated with reduced odds of HT in the general population based on the risk model. Thus, nutritional genomics can help understand the influence of nutrition on metabolic homeostasis pathways and the clinical consequences of hypertension. This study shows the need for healthy, anti-inflammatory, and antioxidant compounds to prevent or treat chronic complications.

Fok I and Bsm I gene polymorphism of vitamin D receptor and essential hypertension: a mechanistic link

“…The truncated protein in individuals with the FF genotype is thought to promote the development of essential hypertension by increasing the production of renin and angiotensin II (Fig. 4 ) [ 47 , 48 ]. The transcriptional activity of the truncated protein is suggested to be higher than that of the full-length protein.…”

“…1,25(OH) 2 D 3 , 1,25-dihydroxyvitamin D; SNP, single nucleotide polymorphism; UTR, untranslated region. Adapted from Nunes et al [ 47 ] with permission from Oxford University Press …”

“…A meta-analysis conducted by Nunes et al [ 47 ] in Brazil reported a significant association of Fok I polymorphism with hypertension. F and f allele frequencies were 55.9 and 44.1% in hypertensive patients, respectively, and 54.3 and 44.7% in control subjects [ 47 ].…”

“…A meta-analysis conducted by Nunes et al [ 47 ] in Brazil reported a significant association of Fok I polymorphism with hypertension. F and f allele frequencies were 55.9 and 44.1% in hypertensive patients, respectively, and 54.3 and 44.7% in control subjects [ 47 ]. However, a meta-analysis conducted in Chinese population by Zhu et al [ 43 ] found no correlation of Fok I polymorphism with susceptibility to hypertension.…”

“…The most notable mechanism linking vitamin D to hypertension is its role as a negative regulator of the RAAS. A meta-analysis study has indicated Fok I polymorphism of the VDR gene results in formation of a truncated protein that evidently increases the synthesis of renin and angiotensin II, thereby promoting the development of hypertension [ 47 ]. Enhanced understanding of the genetic differences in hypertensive population may be a further step in developing individualized treatment strategy.…”