Impact of vitamin D receptor VDR rs2228570 polymorphism in oldest old.
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.


CONCLUSIONS
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.
Department of Physiology, University of Tuebingen, Germany.
Melanie
M
Glocke
Florian
F
Lang
Elke
E
Schaeffeler
Thomas
T
Lang
Matthias
M
Schwab
Undine E
UE
Lang
D000369:Aged, 80 and over; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D016037:Single-Blind Method
D018167:Receptors, Calcitriol