Moon Rebecca J, Harvey Nicholas C, Cooper Cyrus, D'Angelo Stefania, Curtis Elizabeth M, Crozier Sarah R, Barton Sheila J, Robinson Sian M, Godfrey Keith M, Graham Nikki J, Holloway John W, Bishop Nicholas J, Kennedy Stephen, Papageorghiou Aris T, Schoenmakers Inez, Fraser Robert, Gandhi Saurabh V, Prentice Ann, Inskip Hazel M, Javaid M Kassim
Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, United Kingdom.
Paediatric Endocrinology, University Hospitals Southampton National Health Service Foundation Trust, Southampton SO16 6YD, United Kingdom.
J Clin Endocrinol Metab. 2017 Aug 1;102(8):2941-2949. doi: 10.1210/jc.2017-00682.
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.
To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation.
Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.
Hospital antenatal clinics.
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.
1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.
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].
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 < 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.
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.
与维生素D代谢相关基因中的单核苷酸多态性（SNP）已被证明与血清25-羟基维生素D[25(OH)D]浓度有关，但这些关系在产前补充胆钙化醇后尚未得到研究。
确定DHCR7、CYP2R1、CYP24A1和GC基因中的SNP是否与妊娠期补充胆钙化醇的反应相关。
对产前补充胆钙化醇的母亲维生素D骨质疏松症研究试验进行随机分组内分析。
医院产前诊所。
总共纳入了682名白人女性（351名服用安慰剂，331名服用胆钙化醇）。对rs12785878（DHCR7）、rs10741657（CYP2R1）、rs6013897（CYP24A1）和rs2282679（GC）位点的SNP进行基因分型。
从妊娠14周直至分娩，每天补充1000IU胆钙化醇。
在随机分组时和妊娠34周时一次性检测25(OH)D（采用Liaison检测法；DiaSorin公司，英国达特福德）。使用加性模型通过线性回归评估25(OH)D与SNP之间的关联[β表示每增加一个常见等位基因时25(OH)D的变化]。
仅rs12785878（DHCR7）与基线25(OH)D相关[β = 3.1nmol/L；95%置信区间（CI），1.0至5.2nmol/L；P < 0.004]。相比之下，rs10741657（CYP2R1）（β = -5.2nmol/L；95%CI，-8.2至-2.2nmol/L；P = 0.001）和rs2282679（GC）（β = 4.2nmol/L；95%CI，0.9至7.5nmol/L；P = 0.01）与补充后达到的25(OH)D状态相关，而rs12785878和rs6013897（CYP24A1）则不然。
在表皮维生素D生物合成途径中编码7-脱氢胆固醇还原酶的DHCR7基因的遗传变异似乎会改变基线25(OH)D。相比之下，产前补充胆钙化醇的反应与CYP2R1基因中的SNP相关，CYP2R1可能会改变25-羟化酶活性，与GC基因中的SNP也相关，GC可能会影响维生素D结合蛋白的合成或代谢物亲和力。
