Gene · 2018
Triangular relationship between CYP2R1 gene polymorphism, serum 25(OH)D3 levels and T2DM in a Chinese rural population.
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Wang Yan, Yu Fei, Yu Songcheng, Zhang Dongdong, Wang Jun, Han Han, Sun Hualei, Xue Yuan, Ba Yue, Wang Chongjian, Li Wenjie
Аннотация
BACKGROUND: A low serum vitamin D concentration is associated with an increased risk of type 2 diabetes mellitus (T2DM). Recently, several single nucleotid polymorphisms (SNPs) have been identified which influence vitamin D levels. If a causal relationship exists between vitamin D concentrations and T2DM, one would expect a similar association between the newly identified SNPs and T2DM risk. Therefore, this study investigated the association between four SNPs of cytochrome P450 family 2, subfamily R, peptide 1 (CYP2R1) gene, serum 25(OH)D3 levels and T2DM.
METHODS: Three hundred and ninety-seven patients with confirmed T2DM, as well as 397 age- and gender-matched controls were enrolled in this case-control study. Genotyping was performed by TaqMan probe assays. Kruskal-Wallis one-way analysis and muitiple logistic regression analysis were performed to identify the possible risk genotype for vitamin D levels and T2DM, respectively. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-environment interactions.
RESULTS: The serum 25(OH)D3 levels were significant lower in the T2DM group. Significant differences were observed between patients and controls in terms of the genotype distributions of rs1993116 (P = 0.048) and rs10766197 (P = 0.024). Similarly, rs1993116 and rs10766197 polymorphisms were found to be significantly associated with T2DM risk. AG + GG genotype carriers of the rs1993116 and rs10766197 polymorphisms could have an increased risk of developing T2DM compared with AA carriers, the OR and 95% CI were 1.64 (1.09-2.46) and 1.76 (1.18-2.65), respectively. However, none of the tested SNPs were independently associated with serum 25(OH)D3 levels (P > 0.059). Gene-gene and gene-environment interaction analyses indicated that rs12794714-rs10766197 and rs12794714-vitamin D deficiency (VDD) models successfully predicted T2DM risk (P < 0.001).
CONCLUSIONS: Rs1993116 and rs10766197 polymorphisms of CYP2R1 gene may be novel genetic markers for T2DM in China. Given the lack of association between SNPs and serum 25(OH)D3 levels, well-designed future studies should be conducted with larger sample sizes in rural areas of China.
METHODS: Three hundred and ninety-seven patients with confirmed T2DM, as well as 397 age- and gender-matched controls were enrolled in this case-control study. Genotyping was performed by TaqMan probe assays. Kruskal-Wallis one-way analysis and muitiple logistic regression analysis were performed to identify the possible risk genotype for vitamin D levels and T2DM, respectively. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-environment interactions.
RESULTS: The serum 25(OH)D3 levels were significant lower in the T2DM group. Significant differences were observed between patients and controls in terms of the genotype distributions of rs1993116 (P = 0.048) and rs10766197 (P = 0.024). Similarly, rs1993116 and rs10766197 polymorphisms were found to be significantly associated with T2DM risk. AG + GG genotype carriers of the rs1993116 and rs10766197 polymorphisms could have an increased risk of developing T2DM compared with AA carriers, the OR and 95% CI were 1.64 (1.09-2.46) and 1.76 (1.18-2.65), respectively. However, none of the tested SNPs were independently associated with serum 25(OH)D3 levels (P > 0.059). Gene-gene and gene-environment interaction analyses indicated that rs12794714-rs10766197 and rs12794714-vitamin D deficiency (VDD) models successfully predicted T2DM risk (P < 0.001).
CONCLUSIONS: Rs1993116 and rs10766197 polymorphisms of CYP2R1 gene may be novel genetic markers for T2DM in China. Given the lack of association between SNPs and serum 25(OH)D3 levels, well-designed future studies should be conducted with larger sample sizes in rural areas of China.