Sex-specific role of CYP24A1 rs2762939 in the risk of essential hypertension based on the serum vitamin D and total renin concentrations

Varakantham, Varsha; Ale, Kiranmayee; Sailoo, Ashok Kumar Kurakula; Balakrishna, Nagalla; Bharatraj, Dinesh Kumar

doi:10.1016/j.ygeno.2019.05.013

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…Ozben B showed that vitamin D deficiency is related to increase hypertension in healthy individuals, thus they proposed polymorphic enzyme such as CYP24A1 might improve the degradation of active vitamin D and vitamin D deficiency would enhance the risk of stroke development complicating with hypertension (Tarcin et al, 2009). Furthermore, Varakantham et al suggested the SNPs of CYP24A1 gene play a crucial function in disease susceptibility according to influencing the levels of 25(OH)D 3 (Cappellani et al, 2019;Varakantham et al, 2019). Many studies revealed that genetic variants in CYP24A1 gene have previously been investigated in relation to risk of human diseases, such as coronary artery disease (Shen et al, 2010), hypertension (Varakantham et al, 2019), and obesity with ischemic stroke (Turkanoglu Ozcelik et al, 2018) It can be seen CYP24A1 polymorphisms association with ischemic stroke susceptibility.…”

Section: Discussionmentioning

confidence: 99%

The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population

Yang

Wang

et al. 2019

Brain and Behavior

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Aims:Stroke is a complicated neurological disease and the second leading cause of death in the world. We aimed to investigate the association between CYP24A1 genetic polymorphisms and ischemic stroke risk. Methods:In this case-control study, four single-nucleotide polymorphisms of CYP24A1 were selected and genotyped by MassARRAY platform in Chinese Han population. Odds ratios and 95% confidence intervals were calculated via logistic regression analysis with adjustment in genetic models. Results:Our results indicated that CYP24A1 variant (rs1570669) was associated with the decreased risk of ischemic stroke (OR = 0.60, p < .001). Stratification analysis showed that the rs6068816 could enhance the ischemic stroke risk by 1.64 times (OR = 1.64, p = .028), while rs1570669 played protective role (OR = 0.63, p = .044) in age >64 years. The rs2762934 had an increased ischemic stroke susceptibility (OR = 1.62, p = .033); however, rs1570669 might reduce stroke risk (OR = 0.61, p = .015) in age ≤64 years. The rs1570669 depressed ischemic stroke susceptibility both in female and male patients (OR = 0.46, p = .002; OR = 0.69, p = .033, respectively), and rs2296241 would weaken the risk in male (OR = 0.63, p = .012). The rs1570669 was associated with decreased risk of ischemic stroke with hypertension (OR = 0.56, p = .042). Conclusion:Our study gave the evidences that CYP24A1 genetic polymorphisms were significantly associated with ischemic stroke patients, which would provide useful information of assessment or possible diagnostic markers for ischemic stroke. K E Y W O R D SCYP24A1, genetic polymorphisms, ischemic stroke

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Section: Discussionmentioning

confidence: 99%

The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population

Yang

Wang

et al. 2019

Brain and Behavior

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“…Notably, the association between vitamin D-related genes and attempted suicide displayed a sex-dependent difference, which was only appeared among males but not among females. Varsha et al observed a similar sex-specific effect of CYP24A1, indicating it was a risk factor for hypertension in males but a protective factor in females (Varakantham et al, 2020). As there was no significant difference in genotype and allele distribution between males and females in both suicide attempters and community controls (all P values > 0.05) in our study, we speculated that there may be another factor determined by sex, such as sex hormones and sex-related genes, moderate the relationship between vitamin D-related genes and attempted suicide.…”

Section: Discussionmentioning

confidence: 91%

Effects of vitamin D-related gene polymorphisms on attempted suicide

Wei

Liu

Qiu

et al. 2021

Psychiatric Genetics

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Objective Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China.Methods This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. ResultsThe A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. ConclusionsOur findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.

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“…Moreover, a recent study conducted by Varakantham et al suggested the sex-specific role of CYP24A1 genetic variants related to vitamin D metabolism and reported that the risk of hypertension is increased in men with the rs2762939 CC variant; however, this risk of hypertension is decreased in women with the rs2762939 CC variant. This difference is thought to be due to the different effects of CYP24A1 genetic variants on 25(OH)D and renin concentrations in a sex-dependent manner 32 . Overall, males are metabolically vulnerable to lower vascular elasticity compared to females; thus, the vascular elasticity status may not reflect the vitamin D activity.…”

Section: Discussionmentioning

confidence: 99%

Sex and body mass index dependent associations between serum 25-hydroxyvitamin D and pulse pressure in middle-aged and older US adults

Kwak

Choi

2021

Sci Rep

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High pulse pressure (PP) is a valid indicator of arterial stiffness. Many studies have reported that vitamin D concentration is inversely associated with vascular stiffening. This association may differ depending on sex and body mass index (BMI). This study investigated the associations between vitamin D and PP and evaluated whether these associations differ according to sex and BMI, using data for individuals aged ≥ 50 years from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were used as biomarkers of vitamin D levels. High PP was defined as ≥ 60 mmHg. Total 25(OH)D concentrations were dose-dependently associated with lower odds ratios (ORs) for high PP (p-trend = 0.01), after controlling for sociodemographic, behavioral, and dietary factors. When stratified by sex, there was a dose-dependent association between total 25(OH)D concentrations and lower risk of high PP (p-trend < 0.001) in females, but not in males. When stratified by BMI, there was a dose-dependent association between total 25(OH)D concentrations and lower risk of high PP (p-trend < 0.001) in non-overweight subjects, but not in overweight subjects. Improving the vitamin D status could delay elevation of PP and vascular stiffening in female and non-overweight subjects.

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Sex-specific role of CYP24A1 rs2762939 in the risk of essential hypertension based on the serum vitamin D and total renin concentrations

Cited by 7 publications

References 16 publications

The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population

The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population

Effects of vitamin D-related gene polymorphisms on attempted suicide

Sex and body mass index dependent associations between serum 25-hydroxyvitamin D and pulse pressure in middle-aged and older US adults

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