Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study
Background and purpose Low vitamin D levels, measured by serum 25‐hydroxyvitamin D [25(OH)D], are associated with increased stroke risk. Less is known about whether this association differs by race or D binding protein (DBP) single nucleotide polymorphism (SNP) status. Our objective was to character...
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Published in | European journal of neurology Vol. 22; no. 8; pp. 1220 - 1227 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.08.2015
John Wiley & Sons, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Background and purpose
Low vitamin D levels, measured by serum 25‐hydroxyvitamin D [25(OH)D], are associated with increased stroke risk. Less is known about whether this association differs by race or D binding protein (DBP) single nucleotide polymorphism (SNP) status. Our objective was to characterize the associations of and interactions between 25(OH)D levels and DBP SNPs with incident stroke. It was hypothesized that associations of low 25(OH)D with stroke risk would be stronger amongst persons with genotypes associated with higher DBP levels.
Methods
25(OH)D was measured by mass spectroscopy in 12 158 participants in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990–1992, mean age 57 years, 57% female, 23% black) and they were followed through 2011 for adjudicated stroke events. Two DBP SNPs (rs7041, rs4588) were genotyped. Cox models were adjusted for demographic/behavioral/socioeconomic factors.
Results
During a median of 20 years follow‐up, 804 incident strokes occurred. The lowest quintile of 25(OH)D (<17.2 ng/ml) was associated with higher stroke risk [hazard ratio (HR) 1.34 (1.06–1.71) versus highest quintile]; this association was similar by race (P interaction 0.60). There was weak evidence of increased risk of stroke amongst those with 25(OH)D < 17.2 ng/ml and either rs7041 TG/GG [HR = 1.29 (1.00–1.67)] versus TT genotype [HR = 1.19 (0.94–1.52)] (P interaction 0.28) or rs4588 CA/AA [HR = 1.37 (1.07–1.74)] versus CC genotype [HR = 1.14 (0.91–1.41)] (P interaction 0.11).
Conclusions
Low 25(OH)D is a risk factor for stroke. Persons with low 25(OH)D who are genetically predisposed to high DBP (rs7041 G, rs4588 A alleles), who therefore have lower predicted bioavailable 25(OH)D, may be at greater risk for stroke, although our results were not conclusive and should be interpreted as hypothesis generating. |
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Bibliography: | National Heart, Lung, and Blood Institute contracts - No. HHSN268201100005C; No. HHSN268201100006C; No. HHSN268201100007C; No. HHSN268201100008C; No. HHSN268201100009C; No. HHSN268201100010C; No. HHSN268201100011C; No. HHSN268201100012C ark:/67375/WNG-VK418ZCT-P NIH/NHLBI - No. R01HL103706; No. T32HL007024 ArticleID:ENE12731 NIH Office of Dietary Supplements - No. R01HL103706-S1 NIH/NINDS - No. R01NS072243 Table S1. Participant characteristics by race and 25(OH)D quintile, ARIC visit 2 (1990-1992). Table S2. Adjusted hazard ratios (95% confidence intervals) for incident ischaemic stroke and for incident hemorrhagic stroke by 25(OH)D quintile overall; follow-up 1990-1992 through 2011. Table S3. Adjusted hazard ratios (95% confidence intervals) for incident stroke by vitamin D binding protein polymorphism status; follow-up 1990-1992 through 2011. NIH/NIDDK - No. R01DK089174 NHLBI CARe (Candidate Gene Resource) - No. N01HC65226 istex:80FFCD05B89332E3BAF8621C1BE6FE4684D46C8D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1351-5101 1468-1331 1468-1331 |
DOI: | 10.1111/ene.12731 |