CYP3A4 and CYP11A1 variants are risk factors for ischemic stroke: a case control study

Gao, Ning; Tang, Hong; Gao, Ling; Tu, Guolong; Luo, Han; Xia, Ying

doi:10.1186/s12883-020-1628-4

Cited by 8 publications

(3 citation statements)

References 28 publications

(21 reference statements)

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“…Previous studies have demonstrated that these targets are closely related to the occurrence and development of stroke. Indeed, a recent study found that CYP3A4 might be a protective factor for ischemic stroke, while CYP11A1 polymorphism is likely a risk factor for ischemic stroke in the Chinese Han population [ 32 ]. Overall, this D-T network contributes to uncovering the MOA of the ingredients in AGNHW against stroke.…”

Section: Resultsmentioning

confidence: 99%

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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An-Gong-Niu-Huang-Wan (AGNHW) is a well-known formula for treating cerebrovascular diseases, with roles including clearing away heat, detoxification, and wake-up consciousness. In recent years, AGNHW has been commonly used for the treatment of ischemic stroke, but the mechanism by which AGNHW relieves stroke has not been clearly elucidated. In the current study, we developed a multiple systems pharmacology-based framework to identify the potential antistroke ingredients in AGNHW and explore the underlying mechanisms of action (MOA) of AGNHW against stroke from a holistic perspective. Specifically, we performed a network-based method to identify the potential antistroke ingredients in AGNHW by integrating the drug-target network and stroke-associated genes. Furthermore, the oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to validate the anti-inflammatory effects of the key ingredients by determining the levels of inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. The antiapoptotic effects of the key ingredients were also confirmed in vitro. Integrated pathway analysis of AGNHW revealed that it might regulate three biological signaling pathways, including IL-17, TNF, and PI3K-AKT, to play a protective role in stroke. Moreover, 30 key antistroke ingredients in AGNHW were identified via network-based in silico prediction and were confirmed to have known neuroprotective effects. After drug-like property evaluation and pharmacological validation in vitro, scutellarein (SCU) and caprylic acid (CA) were selected for further antistroke investigation. Finally, systems pharmacology-based analysis of CA and SCU indicated that they might exert antistroke effects via the apoptotic signaling pathway and inflammatory response, which was further validated in an in vitro stroke model. Overall, the current study proposes an integrative systems pharmacology approach to identify antistroke ingredients and demonstrate the underlying pharmacological MOA of AGNHW in stroke, which provides an alternative strategy to investigate novel traditional Chinese medicine formulas for complex diseases.

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Section: Resultsmentioning

confidence: 99%

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Ischemic stroke, the most common type of a stroke, is a complex multifactorial disease caused by the interaction between environmental risk factors and genetic predisposition [ 17 , 18 , 19 ]. To date, numerous case-control studies have confirmed the association between SNPs and a stroke [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Ischemic strokes occurring in the carotid circulation are the most common type of an ischemic stroke, accounting for approximately 85% of all cases [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Single-Nucleotide Polymorphisms in Oxidative Stress-Related Genes and the Risk of a Stroke in a Polish Population—A Preliminary Study

et al. 2021

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The present preliminary case-control study was undertaken to detect the potential association of six single nucleotide polymorphisms (SNPs) in oxidative stress-related genes: SOD2 (c.47T > C; rs4880), CAT (c.-89A > T; rs7943316), GPX4 (c.660T > A; rs713041), NOS1 (g.117803515C > T; rs1879417) and NOS2 (c.1823C > T; rs2297518 and c.-227G > C; rs10459953) and the occurrence of a stroke. The SNPs were determined using the TaqMan® Allelic Discrimination Assay in 107 patients with strokes and 107 age- and sex-matched individuals who had not experienced cerebrovascular accidents. The T alleles of the rs4880 were positively correlated with a stroke (bootstrap OR 1.31; 1.07–1.59 95% CI). In the case of the rs713041, an association with the T allele was found (bootstrap OR 1.36; 1.12–1.67). In addition, the occurrence of a stroke was associated with the presence of the C allele of the rs1879417 (bootstrap OR 1.32; 1.09–1.61). We also found that the C/C genotype and C allele of the rs2297518 increased the risk of a stroke (bootstrap ORs 7.00; 4.34–11.29 and 4.96; 3.88–6.34, respectively). Moreover, the C allele of the rs10459953 was associated with an increased occurrence of this disease (bootstrap OR 1.31; 1.08–1.60). These results indicated that genetics variants in the SOD2, GPX4, NOS1 and NOS2 might be associated with susceptibility to strokes in the Polish population.

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“…For instance, a multivariable case-control study showed a positive association of the CYP3A4 rs4646437 polymorphism with the development of hypertension in the Chinese population [ 112 ]. However, a cohort study of Han Chinese individuals showed that the CYP3A4 rs3735451, rs4646440, and rs4646437 polymorphisms were associated with less risk of ischemic stroke [ 113 ]. In a Chinese group of ischemic stroke patients, the CYP3A4*1G allele showed protective effects against clopidogrel resistance [ 114 ].…”

Section: Cyp3a4 Polymorphisms In Various Pat H ...mentioning

confidence: 99%

Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer

et al. 2022

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Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.

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CYP3A4 and CYP11A1 variants are risk factors for ischemic stroke: a case control study

Cited by 8 publications

References 28 publications

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Single-Nucleotide Polymorphisms in Oxidative Stress-Related Genes and the Risk of a Stroke in a Polish Population—A Preliminary Study

Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer

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