{"doi":"10.1210/jc.2017-00682","title":"Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Context</jats:title>\n                  <jats:p>Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Objective</jats:title>\n                  <jats:p>To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Design</jats:title>\n                  <jats:p>Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Setting</jats:title>\n                  <jats:p>Hospital antenatal clinics.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Participants</jats:title>\n                  <jats:p>In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions</jats:title>\n                  <jats:p>1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure</jats:title>\n                  <jats:p>25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele].</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P &amp;lt; 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.</jats:p>\n               </jats:sec>","journal":"The Journal of Clinical Endocrinology &amp; Metabolism","year":2017,"id":684386,"datarank":0.6141516843333151,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.0,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1787961,"name":"Nicholas C Harvey","orcid":null,"position":1,"is_corresponding":false},{"id":109421,"name":"Cyrus Cooper","orcid":"0000-0003-3510-0709","position":2,"is_corresponding":false},{"id":706790,"name":"Stefania D’Angelo","orcid":"0000-0002-7267-1837","position":3,"is_corresponding":false},{"id":1787962,"name":"Elizabeth M Curtis","orcid":null,"position":4,"is_corresponding":false},{"id":1787963,"name":"Sarah R Crozier","orcid":null,"position":5,"is_corresponding":false},{"id":1787964,"name":"Sheila J Barton","orcid":null,"position":6,"is_corresponding":false},{"id":39112,"name":"Sian M Robinson","orcid":null,"position":7,"is_corresponding":false},{"id":706794,"name":"Keith M Godfrey","orcid":"0000-0003-3025-5269","position":8,"is_corresponding":false},{"id":1787966,"name":"Nikki J Graham","orcid":null,"position":9,"is_corresponding":false},{"id":149746,"name":"John W Holloway","orcid":null,"position":10,"is_corresponding":false},{"id":1787967,"name":"Nicholas J Bishop","orcid":null,"position":11,"is_corresponding":false},{"id":298902,"name":"Stephen Kennedy","orcid":"0000-0003-0135-9317","position":12,"is_corresponding":false},{"id":1684273,"name":"Aris T Papageorghiou","orcid":null,"position":13,"is_corresponding":false},{"id":513588,"name":"Inez Schoenmakers","orcid":"0000-0001-9246-538X","position":14,"is_corresponding":false},{"id":185727,"name":"Robert Fraser","orcid":null,"position":15,"is_corresponding":false},{"id":1787968,"name":"Saurabh V Gandhi","orcid":null,"position":16,"is_corresponding":false},{"id":706793,"name":"Ann Prentice","orcid":"0000-0003-0254-6659","position":17,"is_corresponding":false},{"id":1787969,"name":"Hazel M Inskip","orcid":null,"position":18,"is_corresponding":false},{"id":1787970,"name":"M Kassim Javaid","orcid":null,"position":19,"is_corresponding":false},{"id":706791,"name":"Rebecca J Moon","orcid":"0000-0003-2334-2284","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Context</jats:title>\n                  <jats:p>Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Objective</jats:title>\n                  <jats:p>To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Design</jats:title>\n                  <jats:p>Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Setting</jats:title>\n                  <jats:p>Hospital antenatal clinics.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Participants</jats:title>\n                  <jats:p>In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions</jats:title>\n                  <jats:p>1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure</jats:title>\n                  <jats:p>25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele].</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P &amp;lt; 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":4.0943445622221,"endowment":4.0943445622221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28575224","pmcid":"PMC5546866","openalex_id":"https://openalex.org/W2618417661","authors":[],"funders":[{"funder_name":"Versus Arthritis","grant_id":"17702","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_12011/2","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_12011/4","title":null},{"funder_name":"Wellcome Trust","grant_id":"201222/Z/16/Z","title":null},{"funder_name":"National Institute for Health Research 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