Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association With Cytochrome P450 3A Polymorphisms.
Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association With Cytochrome P450 3A Polymorphisms.
复制标题
祖先调整的维生素 D 代谢物浓度与细胞色素 P450 3A 多态性相关。
DOI：
10.1093/aje/kwx187
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发表时间：
2018
影响因子：
5
通讯作者：
Hartman,TerrylJ
中科院分区：
文献类型：
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作者：
Wilson,RobinTaylor;Masters,LorenD;Barnholtz-Sloan,JillS;Salzberg,AnnaC;Hartman,TerrylJ
我们研究了细胞色素P450 （CYP2R1、CYP24A1和CYP3A家族）基因多态性与非夏季血浆维生素D代谢物(25-羟基维生素D3（25（OH)D3）和比例24,25-二羟基维生素D3(24,25（OH)2D3)）浓度之间的关系，年龄匹配（5年内；每个祖先组n= 188）， 2006-2009年）在宾夕法尼亚州中郊区。采用高效液相色谱串联质谱法测定维生素D代谢物。使用配对多元回归和校正最小二乘均值分析来检验基因型和对数转化代谢物浓度之间的相关性，并对年龄、性别、西非遗传血统比例、体重指数、口服避孕药（OC）使用、日光浴床使用、维生素D摄入量、夏至天数、抽血时间、维生素D受体（VDR）和维生素D结合蛋白的同型异构体进行校正。调整后，cyp2r1、CYP3A43、维生素D结合蛋白多态性和遗传祖先比例仍与血浆25(OH) d3相关。只有cyp3a43和vdr多态性与比例24,25(OH)2D3相关。cyp3a43与25(OH) d3的关联程度与日光浴床使用和OC使用相似。发现显著的最小二乘平均相互作用（CYP2R1/OC使用（P= 0.030）和cyp3a43 /VDR(P= 0.013)）。acyp3a43基因型先前与癌症有关，与维生素D代谢的生物标志物密切相关。应进一步研究相互关联。
We investigated the association between genetic polymorphisms in cytochrome P450 (CYP2R1,CYP24A1, and the CYP3A family) with nonsummer plasma concentrations of vitamin D metabolites (25-hydroxyvitamin D3(25(OH)D3) and proportion 24,25-dihydroxyvitamin D3(24,25(OH)2D3)) among healthy individuals of sub-Saharan African and European ancestry, matched on age (within 5 years;n= 188 in each ancestral group), in central suburban Pennsylvania (2006–2009). Vitamin D metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Paired multiple regression and adjusted least-squares mean analyses were used to test for associations between genotype and log-transformed metabolite concentrations, adjusted for age, sex, proportion of West-African genetic ancestry, body mass index, oral contraceptive (OC) use, tanning bed use, vitamin D intake, days from summer solstice, time of day of blood draw, and isoforms of the vitamin D receptor (VDR) and vitamin D binding protein. Polymorphisms inCYP2R1,CYP3A43, vitamin D binding protein, and genetic ancestry proportion remained associated with plasma 25(OH)D3after adjustment. OnlyCYP3A43andVDRpolymorphisms were associated with proportion 24,25(OH)2D3. Magnitudes of association with 25(OH)D3were similar forCYP3A43, tanning bed use, and OC use. Significant least-squares mean interactions (CYP2R1/OC use (P= 0.030) andCYP3A43/VDR(P= 0.013)) were identified. ACYP3A43genotype, previously implicated in cancer, is strongly associated with biomarkers of vitamin D metabolism. Interactive associations should be further investigated.