Triangular relationship between CYP2R1 gene polymorphism, serum 25(OH)D3 levels and T2DM in a Chinese rural population

Wang, Yan; Yu, Fei; Yu, Songcheng; Zhang, Dongdong; Wang, Jun; Han, Han; Sun, Hualei; Xue, Yue; Ba, Yue; Wang, Chongjian; Li, Wenjie

doi:10.1016/j.gene.2018.08.006

Cited by 14 publications

(17 citation statements)

References 27 publications

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“…We previously performed a meta-analysis that synthesized these studies and validated these results [13]. Furthermore, our findings agree with those from a matched case-controlled study that showed that rs1993116 may be a novel genetic contributor to T2DM [11]. Alterations in vitamin D levels resulting from these polymorphisms may influence extracellular calcium concentrations in pancreatic β-cells, which could affect calciumdependent insulin secretion [26].…”

Section: Discussionsupporting

confidence: 80%

“…The locations of rs705117 and rs2282679 in the GC gene and rs12794714, rs19913116, rs10741657, and rs10766197 in the CYP2R1 gene were determined by TaqMan PCR genotyping using an ABI 7500 real-time PCR system (Foster City, CA, USA) as previously described. The thermocycler conditions were as follows: 95 ° C for 10 min, followed by 40 cycles at 95 ° C for 10 s and 60 ° C for 60 s [11].…”

Section: Demographics Anthropometric and Metabolic Characteristicsmentioning

confidence: 99%

“…These changes in affinity may influence the levels of functional 25-hydroxyvitamin D 3 [10]. Candidate gene studies and our previous meta-analysis showed that variants in the GC and CYP2R1 genes significantly influence the risk of T2DM development in Asian populations [11-13].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Associations of GC and CYP2R1 Genes and Gene-Obesity Interactions with Type 2 Diabetes Risk in a Chinese Rural Population

Zhao

Wang

et al. 2020

Ann Nutr Metab

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Introduction: Group-specific component (GC) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene polymorphisms and obesity have been associated with an increased risk for development of type 2 diabetes mellitus (T2DM) in Asian populations. Objective: This study assessed the associations of interactions between GC gene variants and CYP2R1 gene variants and between genes and obesity with T2DM risk. Methods: A study that included 2,271 subjects was performed. Eight single nucleotide polymorphisms in the GC and CYP2R1 genes were genotyped. Interaction analysis was performed using rs7041 in the GC gene and rs1993116 in the CYP2R1 gene. The effects of multiplicative and additive gene-gene and gene-environment interactions on T2DM risk were assessed. Results: The T2DM risk was significantly associated with being overweight/obese, abdominal obesity, rs7041, and rs1993116. A significant additive interaction between rs1993116 and rs7041 was associated with T2DM. In addition, there was a significant multiplicative interaction between rs7041 and body mass index (BMI) associated with elevated blood glucose levels, and at a higher BMI (> 28.47), the G allele carrier showed a stronger effect than the TT genotype. Conclusions: The interactions between GC rs7041-CYP2R1 rs1993116 and GC rs7041-BMI may explain the mechanisms by which these factors increase the risk of T2DM development.

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Section: Discussionsupporting

confidence: 80%

Section: Demographics Anthropometric and Metabolic Characteristicsmentioning

confidence: 99%

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Evaluation of the Associations of GC and CYP2R1 Genes and Gene-Obesity Interactions with Type 2 Diabetes Risk in a Chinese Rural Population

Zhao

Wang

et al. 2020

Ann Nutr Metab

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“…CYP2R1 encodes 25‐hydroxylase which can convert vitamin D into 25(OH)D 45 . Multiple evidences indicated that SNPs in the CYP2R1 gene might affect 25(OH)D concentration and induce disease occurrence and development caused by vitamin D deficiency 20,24,41,46 . Though polymorphisms in rs10766197 were reported to be closely linked to vitamin D deficiency in multiple ethnic populations, 47,48 the 25(OH)D level in this study was not strongly associated with pregnant women carrying the rs10766197 “G” allele and “A” allele.…”

Section: Discussioncontrasting

confidence: 61%

Association between variants in vitamin D‐binding protein gene and vitamin D deficiency among pregnant women in china

Dong

Zhou

Wang

et al. 2020

Clinical Laboratory Analysis

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Background The prevalence of vitamin D deficiency and insufficiency is extremely high in pregnant women worldwide. However, the association between single nucleotide polymorphisms (SNPs) in vitamin D metabolic pathway genes and 25‐hydroxyvitamin D (25(OH)D) concentration among Chinese pregnant women is seldom reported. The risk of adverse neonatal outcomes due to maternal vitamin D deficiency has not been well investigated. Methods A total of 815 pregnant women and 407 infants were enrolled in this study. Serum 25(OH)D concentration was detected. DNA was extracted from the maternal blood for genotyping genetic SNPs in vitamin D pathway. An XGBoost model was established based on SNPs combined with external variables. Results Mean serum 25(OH)D level was 15.67 ± 7.98 ng/mL among the pregnant women. Seventy‐five percent of pregnant women had 25(OH)D deficiency in China. SNPs of GC (rs17467825, rs4588, rs2282679, rs2298850, and rs1155563) were significantly associated with maternal 25(OH)D concentration. The influence of variants of rs17467825, rs4588, rs2282679, and rs2298850 on maternal 25(OH)D might be modified by vitamin D supplementation and sunshine exposure. An XGBoost model was established for monitoring 25(OH)D status in pregnant women and provided clinical advice to reduce the risk of 25(OH)D deficiency. Mothers with 25(OH)D deficiency hinted a risk for macrosomia. Conclusion A high prevalence of vitamin D deficiency in China has been confirmed. A clinical model was established to guide pregnant women to supplement vitamin D according to genotype. Furthermore, we suggest the effect of maternal vitamin D status on the risk of macrosomia.

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“…Among a large group of tested SNPs of CYP2R1 gene, only two of them showed reliable association with the incidence of T2D. However, none of the tested polymorphisms were independently associated with serum 25OHD levels [74].…”

Section: Vitamin D Deficiency and Type 2 Diabetes Mellitusmentioning

confidence: 89%

Vitamin D Deficiency and Diabetes Mellitus

Shymanskyi¹,

Lisakovska²,

Mazanova³

et al. 2020

Vitamin D Deficiency

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Vitamin D (VD) is a molecule that can be synthesized directly in the humans' body or enter the organism with food in the form of inactive precursors. To exert its biological action, VD undergoes two-stage hydroxylation (at the 25th and 1st position) catalyzed by cytochromes P450, the presence of which has already been shown in almost all tissues of the human body. The product of hydroxylation is hormone-active form of vitamin D-1,25(OH) 2 D. 1,25(OH) 2 D binds to specific vitamin D receptor (VDR) and regulates the expression of genes involved in bone remodeling (classical function) and genes that control immune response, hormone secretion, cell proliferation, and differentiation (nonclassical functions). VD deficiency is prevalent around the globe and may be one of the key factors for diabetes development. The direct association between vitamin D deficiency and type 1 (T1D) and type 2 (T2D) diabetes has been proven. Detection of VDR in pancreas and adipose tissue, skeletal muscles, and immune cells allowed implying the antidiabetic role of vitamin D by enhancing insulin synthesis and exocytosis, increasing the expression of the insulin receptor, and modulating immune cells' functions. This chapter summarizes data about relationship between VD insufficiency/deficiency and development of T1D and T2D, and their complications.

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Triangular relationship between CYP2R1 gene polymorphism, serum 25(OH)D3 levels and T2DM in a Chinese rural population

Cited by 14 publications

References 27 publications

Evaluation of the Associations of <b><i>GC</i></b> and <b><i>CYP2R1</i></b> Genes and Gene-Obesity Interactions with Type 2 Diabetes Risk in a Chinese Rural Population

Evaluation of the Associations of <b><i>GC</i></b> and <b><i>CYP2R1</i></b> Genes and Gene-Obesity Interactions with Type 2 Diabetes Risk in a Chinese Rural Population

Association between variants in vitamin D‐binding protein gene and vitamin D deficiency among pregnant women in china

Vitamin D Deficiency and Diabetes Mellitus

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