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Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women.
Clinical Nutrition 2017 November 8
AIMS: To explore the relationship between vitamin D pathway genes, gene-environment interactions and vitamin D level among southeast Chinese pregnant women.
METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester. Information on demographics, lifestyle, and health behavior were collected using a questionnaire. Multilinear regression and logistic regression models were performed to estimate the associations between SNPs and 25(OH)D level.
RESULTS: Mean plasma 25(OH)D concentrations were 15.6 ng/mL among the pregnant women. Variants of GC rs16846876, rs17467825, rs2282679, rs3755967, rs2298850, rs4588, rs7041 and rs1155563, CYP3A4 rs2242480 and CYP24A1 rs2209314 were significantly associated with both 25(OH)D concentrations and vitamin D deficiency (25(OH)D < 15 ng/mL). Variants of NADSYN1/DHCR7 were significantly associated with 25(OH)D concentrations among pregnant women without vitamin D supplements. Pregnant women with vitamin D binding protein (Gc) Gc-1f (P = 0.02) and Gc-1s (P = 0.005) had higher plasma 25(OH)D levels compared to women with Gc-2. Genotype risk score (GRS) calculated from rs7041, rs2242480 and rs2209314 shown a significantly negative association with 25(OH)D levels. Participants with GRS > 3 had a higher risk for vitamin D deficiency than individuals with GRS ≤ 3 (OR = 1.71, 95% CI = 1.25-2.35). Interactions between seasons and CYP27A1 rs933994, CYP3A4 rs2246709 on plasma 25(OH)D concentrations were also observed. Haplotypes of GC and LRP2 genes shown significant associations with 25(OH)D levels among pregnant women, respectively.
CONCLUSIONS: Genetic mutants in vitamin D pathway (GC, CYP3A4, CYP24A1, and NADSYN1/DHCR7) had significant associations with 25(OH)D levels among pregnant women in southeast China. Furthermore, their associations were modified by vitamin D supplementation and season.
METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester. Information on demographics, lifestyle, and health behavior were collected using a questionnaire. Multilinear regression and logistic regression models were performed to estimate the associations between SNPs and 25(OH)D level.
RESULTS: Mean plasma 25(OH)D concentrations were 15.6 ng/mL among the pregnant women. Variants of GC rs16846876, rs17467825, rs2282679, rs3755967, rs2298850, rs4588, rs7041 and rs1155563, CYP3A4 rs2242480 and CYP24A1 rs2209314 were significantly associated with both 25(OH)D concentrations and vitamin D deficiency (25(OH)D < 15 ng/mL). Variants of NADSYN1/DHCR7 were significantly associated with 25(OH)D concentrations among pregnant women without vitamin D supplements. Pregnant women with vitamin D binding protein (Gc) Gc-1f (P = 0.02) and Gc-1s (P = 0.005) had higher plasma 25(OH)D levels compared to women with Gc-2. Genotype risk score (GRS) calculated from rs7041, rs2242480 and rs2209314 shown a significantly negative association with 25(OH)D levels. Participants with GRS > 3 had a higher risk for vitamin D deficiency than individuals with GRS ≤ 3 (OR = 1.71, 95% CI = 1.25-2.35). Interactions between seasons and CYP27A1 rs933994, CYP3A4 rs2246709 on plasma 25(OH)D concentrations were also observed. Haplotypes of GC and LRP2 genes shown significant associations with 25(OH)D levels among pregnant women, respectively.
CONCLUSIONS: Genetic mutants in vitamin D pathway (GC, CYP3A4, CYP24A1, and NADSYN1/DHCR7) had significant associations with 25(OH)D levels among pregnant women in southeast China. Furthermore, their associations were modified by vitamin D supplementation and season.
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