Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study

被引：40

作者：

Magnus, Maria C. ^{[1
,2
,3
]}

Miliku, Kozeta ^{[4
,5
,6
]}

Bauer, Anna ^{[7
]}

Engel, Stephanie M. ^{[7
]}

Felix, Janine F. ^{[4
,5
,6
]}

Jaddoe, Vincent W. V. ^{[4
,5
,6
]}

Lawlor, Debbie A. ^{[1
,2
,8
,9
]}

London, Stephanie J. ^{[10
]}

Magnus, Per ^{[3
]}

McGinnis, Ralph ^{[11
]}

Nystad, Wenche ^{[12
]}

Page, Christian M. ^{[12
,13
]}

Rivadeneira, Fernando ^{[4
,6
,14
]}

Stene, Lars C. ^{[12
]}

Tapia, German ^{[12
]}

Williams, Nicholas ^{[11
]}

Bonilla, Carolina ^{[1
,2
,15
]}

Fraser, Abigail ^{[1
,2
,8
,9
]}

机构：

[1] Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

[2] Univ Bristol Sch Med, Dept Populat Hlth Sci, Bristol, Avon, England

[3] Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway

[4] Erasmus MC, Univ Med Ctr Rotterdam, Generat Study Grp R, Rotterdam, Netherlands

[5] Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands

[6] Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands

[7] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA

[8] Univ Hosp Bristol NHS Fdn Trust, Bristol Biomed Res Ctr, Natl Inst Hlth Res, Bristol, Avon, England

[9] Univ Bristol, Bristol, Avon, England

[10] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA

[11] Univ Cambridge, Sanger Inst, Cambridge, England

[12] Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway

[13] Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway

[14] Erasmus MC, Univ Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands

[15] Univ Sao Paulo, Fac Med, Dept Med Prevent, Sao Paulo, Brazil

来源：

BMJ-BRITISH MEDICAL JOURNAL | 2018年 / 361卷

基金：

欧盟地平线“2020”;

关键词：

1,25-DIHYDROXYVITAMIN D-3; NEONATAL OUTCOMES; D SUPPLEMENTATION; PREECLAMPSIA; WOMEN; DETERMINANTS; ASSOCIATION; INSTRUMENTS; COHORT;

D O I：

10.1136/bmj.k2167

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVE To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN One and two sample mendelian randomisation analyses. SETTING Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels < 25 nmol/L compared with >= 75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for preeclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level < 75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels < 50 nmol/L. CONCLUSIONS No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with preeclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.

引用

页数：9

共 42 条

[1]

Lower Serum Vitamin D Metabolite Levels in Relation to Circulating Cytokines/Chemokines and Metabolic Hormones in Pregnant Women with Hypertensive Disorders [J].