Molecular Genetics Department, Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Clin Lab Anal. 2021 Feb;35(2):e23617. doi: 10.1002/jcla.23617. Epub 2020 Oct 14.
The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25-dihydroxyvitamin D3, which starts with a 25-hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α-hydroxylation via CYP27B1.
By using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non-cancer controls. The genotyping was performed using tetra-primer amplification refractory mutation system polymerase chain reaction (TP-ARMS-PCR) method.
The results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039).
CYP2R1 and CYP27B1 genes were over-expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.
细胞色素 P450 是一个超家族的酶，控制生物活性形式的维生素 D 的合成，1,25-二羟维生素 D3。这些酶有助于 1,25-二羟维生素 D3 的形成，这始于 CYP2R1 和 CYP27A1 的 25-羟化作用和 CYP27B1 的随后 1α-羟化作用。
通过使用定量实时聚合酶链反应（qRT-PCR），我们分析了维生素 D 代谢途径中 CYP2R1、CYP27A1 和 CYP27B1 基因的表达比例，共分析了 75 例结直肠癌（CRC）组织与相邻组织相比。此外，我们评估了 CYP27B1 rs4646536 和 CYP2R1 rs12794714 和 rs10766196 多态性与 490 例受试者（包括 245 例 CRC 患者和 245 例非癌症对照）CRC 风险的相关性。基因分型采用四引物扩增受阻突变系统聚合酶链反应（TP-ARMS-PCR）方法进行。
结果表明，与相邻组织相比，CYP2R1 和 CYP27B1 基因在结直肠癌组织中分别上调了 2.3 和 2.7 倍。rs12794714 AG 基因型增加了 CRC 的风险（P=0.03）。此外，在显性遗传模型下观察到显著的相关性（P=0.039）。
与相邻对照组织相比，CYP2R1 和 CYP27B1 基因在 CRC 样本中过度表达。此外，CYP2R1 rs12794714 变体与研究样本中 CRC 的风险相关。CYP2R1 rs10766196 和 CYP27B1 rs4646536 分别与 CYP2R1 和 CYP27B1 基因表达改变无关，但 CYP2R1 rs12794714 多态性可能是 CYP2R1 上调的原因，并增加了 CRC 的风险。
