Impact of Vitamin D Receptor VDR rs2228570 Polymorphism in Oldest Old

Abstract

Background: Calcitriol, a key player in the regulation of mineral metabolism, influences, directly or by increasing plasma Ca²⁺ and phosphate levels, a multitude of physiological functions, such as bone mineralization, cell proliferation, immune response, carbohydrate metabolism, blood pressure, platelet reactivity, gastric acid secretion, cognitive function and mood. Calcitriol is mainly effective by stimulation of the Vitamin D receptor VDR. The responsiveness of VDR may be affected by gene variants, such as the FokI polymorphism (rs2228570). The GG gene variant is expected to be more active than the GA or AA gene variant. The present study explored the impact of VDR rs2228570 on survival and health of oldest old individuals (> 90 years). Methods: 101 individuals > 90 years were examined and genotyped. As a result, the prevalence of GG, GA & AA was 36 (10 ♂, 26♀), 52 (24 ♂, 28♀) and 13 (4 ♂, 9♀), respectively, a prevalence not significantly different from the frequency in public available dbSNP and a population (n = 208) of young volunteers (average age 49 years). Results: As compared to carriers of GG, carriers of AA and/or GA displayed significantly (p<0.05) lower diastolic blood pressure (significant only in ♂), higher instrumental activity of daily life (IADL) score and more frequent hospital visits (significant only in ♂), significantly lower prevalence of depression (significant in ♀+♂), renal disease (significant only in ♀), allergy, peptic ulcer and urolithiasis (significant only in ♂), as well as significantly higher prevalence of transitoric ischemic attacks. In a younger population a German version of the NEO-FFI, allowing reliable and valid assessment of personality, revealed decreased neuroticism (significant only in ♂) and increased extraversion in AA carriers. Conclusion: The Vitamin D receptor gene variant VDR rs2228570 has only little impact on life span but may affect a variety of pathophysiologically relevant functions including mood.

The association of VDR polymorphisms and type 2 diabetes in older people living in community in Santiago de Chile

“…There is controversy in the literature about the different impact of FokI SNP in different populations, with some populations not showing association with T2D and other conditions 5 , 41 – 43 . This could be attributed to different penetrance, however, a recent meta-analysis found statistical evidence that the C allele of the FokI polymorphism in the VDR gene may be an allele of susceptibility to T2D, especially among Asian populations, but not the BsmI, ApaI and TaqI polymorphisms 44 .…”

Glia in the cytokine-mediated onset of depression: fine tuning the immune response

“…Despite the substantial amount of evidence linking VDR and the immune response, its role in the regulation of the inflammatory response in mood disorders remains to be elucidated. Only two studies to date have reported an association between VDR gene variant and susceptibility to develop depressive symptoms in old age (Kuningas et al, 2009 ; Glocke et al, 2013 ). Moreover, studies evaluating the relationship of vitamin D and the cytokine network in mood disorders fall short of expectations.…”

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

“…The haplotype on chromosome 12 located between 48 159 721 -48 263 828 bp overlapped with four gene coding regions. One of these encodes the vitamin D receptor (VDR) for which there is a suggestive association with MDD, [59][60][61] however this association appears to be population dependant. 62 The discovery cohort was based in Scotland which is at a latitude of approximately 55° to 60°N and is a country known for its rather cloudy and inclement climate.…”