SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation: A randomized clinical trial

Mingzhi Zhang, Lan Juan Zhao, Yu Zhou, Rhamee Badr, Patrice Watson, An Ye, Boting Zhou, Jigang Zhang, Hong Wen Deng, Robert R. Recker, Joan M. Lappe

Research output: Contribution to journalArticle

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Abstract

The level of serum 25-Hydroxyvitamin D [25(OH)D] has high heritability, suggesting that genes may contribute to variations in serum 25(OH)D level and vitamin D dose-response. As vitamin D deficiency has been linked to numerous diseases, understanding how genetic variation contributes to vitamin D dose-response is important for personalized vitamin D treatment and cost-effective disease prevention. To identify genetic variants responsible for vitamin D status and dose-response, we performed two vitamin D3 and calcium clinical supplementation trials in 2,207 postmenopausal Caucasian women. We examined the association of 291 SNPs with baseline serum 25(OH)D levels and 25(OH)D dose-response. Five SNPs, rs10500804 (P = 4.93 × 10 â '7), rs2060793 (P = 6.63 × 10 â '7), rs10741657 (P = 1.49 × 10 â '6), rs10766197 (P = 1.05 × 10 â '5) and rs11023380 (P = 7.67 × 10 â '5) in the CYP2R1 gene, as well as 6 SNPs, rs4588 (P = 7.86 × 10 â '7), rs2298850 (P = 1.94 × 10 â '6), rs1155563 (P = 6.39 × 10 â '6), rs705119 (P = 2.80 × 10 â '5), rs705120 (P = 1.08 × 10 â '4) and rs222040 (P = 1.59 × 10 â '4) in the GC gene were associated with baseline serum 25(OH)D levels. SNP rs11185644 near the RXRA was significantly associated with 25(OH)D dose-response (P = 1.01 × 10 â '4). Our data suggest that polymorphisms in the CYP2R1 and GC gene may contribute to variation in baseline serum 25(OH)D concentration, and that polymorphism rs11185644 may contribute to variation in 25(OH)D dose-response in healthy postmenopausal Caucasian women.

Original languageEnglish (US)
Article number40593
JournalScientific Reports
Volume7
DOIs
StatePublished - Jan 12 2017

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Cholecalciferol
Single Nucleotide Polymorphism
Randomized Controlled Trials
Vitamin D
Serum
Genes
Cost of Illness
Vitamin D Deficiency
Health Care Costs
Clinical Trials
Calcium

All Science Journal Classification (ASJC) codes

  • General

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SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation : A randomized clinical trial. / Zhang, Mingzhi; Zhao, Lan Juan; Zhou, Yu; Badr, Rhamee; Watson, Patrice; Ye, An; Zhou, Boting; Zhang, Jigang; Deng, Hong Wen; Recker, Robert R.; Lappe, Joan M.

In: Scientific Reports, Vol. 7, 40593, 12.01.2017.

Research output: Contribution to journalArticle

Zhang, Mingzhi ; Zhao, Lan Juan ; Zhou, Yu ; Badr, Rhamee ; Watson, Patrice ; Ye, An ; Zhou, Boting ; Zhang, Jigang ; Deng, Hong Wen ; Recker, Robert R. ; Lappe, Joan M. / SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation : A randomized clinical trial. In: Scientific Reports. 2017 ; Vol. 7.
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title = "SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation: A randomized clinical trial",
abstract = "The level of serum 25-Hydroxyvitamin D [25(OH)D] has high heritability, suggesting that genes may contribute to variations in serum 25(OH)D level and vitamin D dose-response. As vitamin D deficiency has been linked to numerous diseases, understanding how genetic variation contributes to vitamin D dose-response is important for personalized vitamin D treatment and cost-effective disease prevention. To identify genetic variants responsible for vitamin D status and dose-response, we performed two vitamin D3 and calcium clinical supplementation trials in 2,207 postmenopausal Caucasian women. We examined the association of 291 SNPs with baseline serum 25(OH)D levels and 25(OH)D dose-response. Five SNPs, rs10500804 (P = 4.93 × 10 {\^a} '7), rs2060793 (P = 6.63 × 10 {\^a} '7), rs10741657 (P = 1.49 × 10 {\^a} '6), rs10766197 (P = 1.05 × 10 {\^a} '5) and rs11023380 (P = 7.67 × 10 {\^a} '5) in the CYP2R1 gene, as well as 6 SNPs, rs4588 (P = 7.86 × 10 {\^a} '7), rs2298850 (P = 1.94 × 10 {\^a} '6), rs1155563 (P = 6.39 × 10 {\^a} '6), rs705119 (P = 2.80 × 10 {\^a} '5), rs705120 (P = 1.08 × 10 {\^a} '4) and rs222040 (P = 1.59 × 10 {\^a} '4) in the GC gene were associated with baseline serum 25(OH)D levels. SNP rs11185644 near the RXRA was significantly associated with 25(OH)D dose-response (P = 1.01 × 10 {\^a} '4). Our data suggest that polymorphisms in the CYP2R1 and GC gene may contribute to variation in baseline serum 25(OH)D concentration, and that polymorphism rs11185644 may contribute to variation in 25(OH)D dose-response in healthy postmenopausal Caucasian women.",
author = "Mingzhi Zhang and Zhao, {Lan Juan} and Yu Zhou and Rhamee Badr and Patrice Watson and An Ye and Boting Zhou and Jigang Zhang and Deng, {Hong Wen} and Recker, {Robert R.} and Lappe, {Joan M.}",
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AU - Zhang, Mingzhi

AU - Zhao, Lan Juan

AU - Zhou, Yu

AU - Badr, Rhamee

AU - Watson, Patrice

AU - Ye, An

AU - Zhou, Boting

AU - Zhang, Jigang

AU - Deng, Hong Wen

AU - Recker, Robert R.

AU - Lappe, Joan M.

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