BACKGROUND: Decreased circulating 25-hydroxy-vitamin D (25-OH-vitamin D) concentrations have been associated with mortality rates, but it is unclear whether this association is causal. We performed a Mendelian randomization study and analyzed whether 3 common single-nucleotide polymorphisms (SNPs) associated with 25-OH-vitamin D concentrations are causal for mortality rates. METHODS: Genotypes of SNPs in the group-specific component gene (GC, rs2282679), 7-dehydrocholesterol reductase gene (DHCR7, rs12785878), and cytochrome P450 IIR-1 gene (CYP2R1, rs10741657) were determined in a prospective cohort study of 3316 male and female participants [mean age 62.6 (10.6) years] scheduled for coronary angiography between 1997 and 2000. 25-OH-vitamin D concentrations were determined by RIA. The main outcome measures were all-cause deaths, cardiovascular deaths, and noncardiovascular deaths. RESULTS: In a linear regression model adjusting for month of blood sampling, age, and sex, vitamin D concentrations were predicted by GC genotype (P < 0.001), CYP2R1 genotype (P = 0.068), and DHCR7 genotype (P < 0.001), with a coefficient of determination (r(2)) of 0.175. During a median follow-up time of 9.9 years, 955 persons (30.0%) died, including 619 deaths from cardiovascular causes. In a multivariate Cox regression adjusted for classical risk factors, GC, CYP2R1, and DHCR7 genotypes were not associated with all-cause mortality, cardiovascular mortality, or noncardiovascular mortality. CONCLUSIONS: Genetic variants associated with 25-OH-vitamin D concentrations do not predict mortality. This suggests that low 25-OH-vitamin D concentrations are associated with, but unlikely to be causal for, higher mortality rates.
BACKGROUND: Decreased circulating 25-hydroxy-vitamin D (25-OH-vitamin D) concentrations have been associated with mortality rates, but it is unclear whether this association is causal. We performed a Mendelian randomization study and analyzed whether 3 common single-nucleotide polymorphisms (SNPs) associated with 25-OH-vitamin D concentrations are causal for mortality rates. METHODS: Genotypes of SNPs in the group-specific component gene (GC, rs2282679), 7-dehydrocholesterol reductase gene (DHCR7, rs12785878), and cytochrome P450 IIR-1 gene (CYP2R1, rs10741657) were determined in a prospective cohort study of 3316 male and female participants [mean age 62.6 (10.6) years] scheduled for coronary angiography between 1997 and 2000. 25-OH-vitamin D concentrations were determined by RIA. The main outcome measures were all-cause deaths, cardiovascular deaths, and noncardiovascular deaths. RESULTS: In a linear regression model adjusting for month of blood sampling, age, and sex, vitamin D concentrations were predicted by GC genotype (P < 0.001), CYP2R1 genotype (P = 0.068), and DHCR7 genotype (P < 0.001), with a coefficient of determination (r(2)) of 0.175. During a median follow-up time of 9.9 years, 955 persons (30.0%) died, including 619 deaths from cardiovascular causes. In a multivariate Cox regression adjusted for classical risk factors, GC, CYP2R1, and DHCR7 genotypes were not associated with all-cause mortality, cardiovascular mortality, or noncardiovascular mortality. CONCLUSIONS: Genetic variants associated with 25-OH-vitamin D concentrations do not predict mortality. This suggests that low 25-OH-vitamin D concentrations are associated with, but unlikely to be causal for, higher mortality rates.
Authors: Anders H Berg; Camille E Powe; Michele K Evans; Julia Wenger; Guillermo Ortiz; Alan B Zonderman; Pirianthini Suntharalingam; Kathryn Lucchesi; Neil R Powe; S Ananth Karumanchi; Ravi I Thadhani Journal: Clin Chem Date: 2015-04-28 Impact factor: 8.327
Authors: Stefan Pilz; Nicolas Verheyen; Martin R Grübler; Andreas Tomaschitz; Winfried März Journal: Nat Rev Cardiol Date: 2016-05-06 Impact factor: 32.419
Authors: Louie Mar A Gangcuangco; Dominic C Chow; Chin-Yuan Liang; Beau K Nakamoto; Tracie M Umaki; Kalpana J Kallianpur; Cecilia M Shikuma Journal: Hawaii J Med Public Health Date: 2013-06
Authors: Roger Bouillon; Claudio Marcocci; Geert Carmeliet; Daniel Bikle; John H White; Bess Dawson-Hughes; Paul Lips; Craig F Munns; Marise Lazaretti-Castro; Andrea Giustina; John Bilezikian Journal: Endocr Rev Date: 2019-08-01 Impact factor: 19.871
Authors: Jue-Sheng Ong; Gabriel Cuellar-Partida; Yi Lu; Peter A Fasching; Alexander Hein; Stefanie Burghaus; Matthias W Beckmann; Diether Lambrechts; Els Van Nieuwenhuysen; Ignace Vergote; Adriaan Vanderstichele; Jennifer Anne Doherty; Mary Anne Rossing; Jenny Chang-Claude; Ursula Eilber; Anja Rudolph; Shan Wang-Gohrke; Marc T Goodman; Natalia Bogdanova; Thilo Dörk; Matthias Dürst; Peter Hillemanns; Ingo B Runnebaum; Natalia Antonenkova; Ralf Butzow; Arto Leminen; Heli Nevanlinna; Liisa M Pelttari; Robert P Edwards; Joseph L Kelley; Francesmary Modugno; Kirsten B Moysich; Roberta B Ness; Rikki Cannioto; Estrid Høgdall; Claus K Høgdall; Allan Jensen; Graham G Giles; Fiona Bruinsma; Susanne K Kjaer; Michelle At Hildebrandt; Dong Liang; Karen H Lu; Xifeng Wu; Maria Bisogna; Fanny Dao; Douglas A Levine; Daniel W Cramer; Kathryn L Terry; Shelley S Tworoger; Meir Stampfer; Stacey Missmer; Line Bjorge; Helga B Salvesen; Reidun K Kopperud; Katharina Bischof; Katja Kh Aben; Lambertus A Kiemeney; Leon Fag Massuger; Angela Brooks-Wilson; Sara H Olson; Valerie McGuire; Joseph H Rothstein; Weiva Sieh; Alice S Whittemore; Linda S Cook; Nhu D Le; C Blake Gilks; Jacek Gronwald; Anna Jakubowska; Jan Lubiński; Tomasz Kluz; Honglin Song; Jonathan P Tyrer; Nicolas Wentzensen; Louise Brinton; Britton Trabert; Jolanta Lissowska; John R McLaughlin; Steven A Narod; Catherine Phelan; Hoda Anton-Culver; Argyrios Ziogas; Diana Eccles; Ian Campbell; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Susan J Ramus; Anna H Wu; Agnieszka Dansonka-Mieszkowska; Jolanta Kupryjanczyk; Agnieszka Timorek; Lukasz Szafron; Julie M Cunningham; Brooke L Fridley; Stacey J Winham; Elisa V Bandera; Elizabeth M Poole; Terry K Morgan; Harvey A Risch; Ellen L Goode; Joellen M Schildkraut; Celeste L Pearce; Andrew Berchuck; Paul Dp Pharoah; Georgia Chenevix-Trench; Puya Gharahkhani; Rachel E Neale; Penelope M Webb; Stuart MacGregor Journal: Int J Epidemiol Date: 2016-09-04 Impact factor: 7.196