Posted on 11/14/2012 10:15:09 PM PST by neverdem
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
 |
Variations in the vitamin D receptor gene may influence the clinical effects of low vitamin D levels in some chronic diseases, researchers found.
Among patients with low serum 25-hydroxyvitamin D (25(OH)D) in a U.S.-based cohort, the presence of one risk allele at rs7968585 was associated with a 40% increased risk for potentially fatal composite clinical outcomes, including hip fracture, myocardial infarction, cancer, and death (hazard ratio 1.40, 95% CI 1.12 to 1.74) according to Gregory Levin, PhD, of the University of Washington in Seattle, and colleagues.
The presence of two risk alleles was linked with an 82% increased risk (HR 1.82, 95% CI 1.31 to 2.54), they said.
However, patients in the cohort without the polymorphism showed no association between low 25(OH)D and these outcomes (HR 0.93, 95% CI 0.70 to 1.24), they wrote online in the Journal of the American Medical Association.
"The totality of these findings suggests that low [25(OH)D] concentration may be a modifiable risk factor for many chronic diseases," they wrote.
The researchers analyzed genetic variations in 304 patients with low 25(OH)D compared with 1,210 patients with normal concentrations enrolled in the Cardiovascular Health Study. They looked at the potential effects of those genetic variations on major health outcomes at 15 years of follow-up (median of 11 years).
Participants were white and mostly female (70%) with a mean age of 74, a mean 25(OH)D concentration of 26.7 ng/mL. They had a higher mean body mass index and were more likely to have diabetes or hypertension than those with normal vitamin D concentrations.
A total 948 participants (63%) experienced an event by the 15-year follow-up. Low 25(OH)D was associated with a 32% increased HR for composite adverse outcome (95% CI 1.13 to 1.54).
Without accounting for vitamin D concentration, the authors said there was no evidence in the cohort of main effect associations between either rs7968585 (HR per additional minor allele, 1.00, 95% CI 0.91 to 1.06, P=0.93) or rs2239179 (HR 0.93, 95% CI 0.85 to 1.02, P=0.13) and risk of the composite outcome.
The authors conducted a replication meta-analysis based on data from three additional cohorts -- the U.S. Health, Aging, and Body Composition (Health ABC) study, the Italian Invecchiare in Chianti, and the Swedish Uppsala Longitudinal Study of Adult Men.
Estimates for associations between low 25(OH)D and composite outcomes "were in the same direction in all four cohorts, but statistical significance was attained only in the Health ABC cohort."
Additional copies of risk alleles at rs7968585 were associated with an HR of 1.22 (95% CI 1.09 to 1.36) in the meta-analysis, they wrote.
"These results suggest that individuals with specific [25(OH)D] metabolism genotypes may be particularly susceptible to, or protected from, the potential adverse health effects of low vitamin D," they concluded.
The authors noted the study was limited by some heterogeneity in estimated interactions, lack of functional data to explore why variations affect 25(OH)D concentrations, lack of long-term measurements of 25(OH)D concentrations, and lack of generalizability of the study populations.
Also, genetic information was derived from single-nucleotide polymorphisms measured in whole genome chip platforms, which cannot identify potential causal variants.
The Cardiovascular Health Study was funded by grants from the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Center for Research Resources, the National Institute of Diabetes and Digestive and Kidney Diseases, and NIH.
The Health, Aging, and Body Composition study was funded by grants from the National Institute on Aging.
The genome-wide association study was funded by grants from the National Institute on Aging and NIH.
The baseline Invecchiare in Chianti study was supported by the Italian Ministry of Health, the National Institute on Aging, and NIH.
The Uppsala Longitudinal Study of Adult Men was supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Thureus Foundation, and Uppsala University.
Study authors declared various relationships (grants, lecture fees, consulting, pending patents, safety monitoring, steering committee) for Abbott Laboratories, National Institute on Aging, NIH, American Society for Nutrition, the Department of Veteran Affairs, Abbott Nutrition Health Institute, Diasorin, Genzyme, Lultpold, Mitsubishi, Cyyovhtoma, Astellas, Kal, Shire, Amgen, Zoll ZifeCot, and Medtronic.
Primary source: Journal of the American Medical Association
Source reference:
Levin GP, et al "Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes" JAMA 2012; 308: 1898-1905.
Well.. effin’ D’oh!
Half of the country gets no sun October thru April.
Very interesting
Sunlight is not the only source of vitamin D.
Vitamin D ping
Is’nt cod liver oil loaded with natural vitamin D?
The article is about variations in the vitamin D receptors caused by genetic differences.
Get some sun - don't use sunscreen unless you will be in the sun for >15 minutes.
Here’s how I see it through my own condition. The bad gene isn’t allowing the vitamin D that one takes in to convert to *active vitamin D* that the body uses.
Granted, I could be misinterpretting what I read.
I deal with hypoparathyroidism due to my pararthyroid glands getting damaged during thyroid surgeries. In laymen’s terms, the vitamin D I take in can’t be converted to active vitamin D that the body uses. No additional amount of sun or supplements helps. It’ll sit in my body unmetabolized.
Where all this becomes a problem is with my blood serum - calcium in my blood. Again, thanks to the thyroid surgeries, my blood serum gets down to dangerous levels: hypocalcemia. I need to take loads of calcium for it but for that to metabolize properly, I need active vitamin D.
So in a nutshell, I have to take a prescription called calcitriol (active vitamin D) for the rest of my life in order to keep the calcium in my blood stable.
For what it’s worth, back to the article, when my calcium is low, my blood pressure goes up. Get decent about of calcium in and the blood pressure goes down.
I used to have four or five a year, typically lasting a week or more. Since upping Vit D to 10K units daily a couple of years back, I think I might have had ONE, (and that mild). Since many of these colds resulted in sinus infections, Dr's visits, antibiotics, etc., that alone was worth it.
Ditto for me. Taking a daily 5000k dose of vitamin D has dramatically reduced the number of times I get sick per year. Basically, I don’t get colds now (knock on wood).
The part I don't understand is why it takes some as little as 48 hours to get relief, while it takes other several months (even taking loading doses of 50K IU once a week in addition to the regular 10-20K IU).
The article also says that when levels of D are not accounted for, then the statistical significance of the association between the risk alleles and the adverse outcomes is removed.
Conditioning on statistical variables can induce associations known as spurious correlations often discussed in statistical literature under Simpson’s Paradox. Many medical researchers, even those backed by biostatisticians, are oblivious if not ignorant to such mathematical paradoxes that lead to false conclusions. The hunt for statistical significance is tantamount to a continuation of research funding. Spurious associations can be good for funding and not necessarily good for science.
So acapesket’s questioning of regional sunlight effects could be notable; maybe, maybe not. A subgroup analysis accounting for geographic location could reveal more on the association’s possible validity.
I would not immediately draw the conclusion that geographical location is a surrogate for low D levels since many foods are D enriched.
Most notable about the study is the integration of biotechnology into the data acquisition process. However, such technology generates more things to look at that are tied to the same problem, and hence more things that can under faulty analysis generate more false associations.
We need statistical philosophers working with technologists to come up with more consistent design and analysis methods.
Vitamin D is a very important item. Too much and it decreases your life span; too little and it allows all sorts of maladies to appear.
And it all starts with cholesterol. Expose cholesterol to sunlight (UV) and it will spontaneously change in vitamin D (they don’t actually add vitamin D to milk they irradiate the milk with UV to make it). Vitamin D and phosphorus and calcium all need to be present to grow bones, but the same 3 items (Vit D, phosphorus and calcium) can also be used to make virtually all the steroids, pain killers, hormones and control chemicals your body uses to maintain itself. And to make matters even more confusing, nobody really knows how much is the right amount; ther are opinions, but they are only that, opinions.
Recently, scientists have found that the immunity-benefits with vitamin D—from sunlight—is far more valuable than the skin cancer risk.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.