Ding-Yuan Liu1, Ren-Yan Li2, Li-Juan Fu3, Enoch Appiah Adu-Gyamfi1, Yin Yang4, Ying Xu4, Le-Tian Zhao2, Tian-Feng Zhang2, Hua-Qiong Bao5, Xiao-Ou Xu5, Xiao-Han Gao2, Xue-Niu Yang6, Yu-Bin Ding7. 1. The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Department of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. 2. NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 401120, People's Republic of China. 3. Department of Pharmacology, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China. 4. Department of Epidemiology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. 5. Affiliated Hospital of Chongqing Academy of Population and Family Planning, Chongqing, 400020, People's Republic of China. 6. Affiliated Hospital of Chongqing Academy of Population and Family Planning, Chongqing, 400020, People's Republic of China. 785794729@qq.com. 7. The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Department of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China. dingyb@cqmu.edu.cn.
Abstract
PURPOSE: Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. METHODS: This case-control study enrolled 75 RSA patients and 83 controls. Serum VD and some cytokines were detected with LC-MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. RESULTS: The results revealed a significant correlation between the AG genotype of CYP2R1 rs12794714 and VD levels (OR 0.686; 95% CI 0.49-0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1 rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683-1023.265, 3.110-1138.367; p = 0.009, 0.007, respectively). CONCLUSION: Our results indicate that CYP2R1 rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1 rs12794714 is necessary to warrant proactive counseling and treatment against RSA.
PURPOSE:Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. METHODS: This case-control study enrolled 75 RSApatients and 83 controls. Serum VD and some cytokines were detected with LC-MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. RESULTS: The results revealed a significant correlation between the AG genotype of CYP2R1rs12794714 and VD levels (OR 0.686; 95% CI 0.49-0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683-1023.265, 3.110-1138.367; p = 0.009, 0.007, respectively). CONCLUSION: Our results indicate that CYP2R1rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1rs12794714 is necessary to warrant proactive counseling and treatment against RSA.
Authors: Jeffrey B Cheng; Michael A Levine; Norman H Bell; David J Mangelsdorf; David W Russell Journal: Proc Natl Acad Sci U S A Date: 2004-05-05 Impact factor: 11.205