Genetic polymorphism of CYP4A11 and CYP4A22 genes and in silico insights from comparative 3D modelling in a French population

Cardenas, Christian L. Lino; Renault, Nicolas; Farce, Amaury; Cauffiez, Christelle; Allorge, Delphine; Lo-Guidice, Jean-Marc; Lhermitte, Michel; Chavatte, Philippe; Broly, Franck; Chevalier, Dany

doi:10.1016/j.gene.2011.07.015

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…CYP4A22 (AF208532) is homologous to the CYP4A11 gene sharing 96% of overall nucleotide sequence identity (Bellamine et al, 2003). An SNP (g.4628G>A, p.Gly130Ser) was identified in CYP4A22 exon 3, which confers an amino acid change from glycine to serine (Cardenas et al, 2011), resulting in a non-functional protein (Gainer et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China

Liang¹,

Yan²,

Suyila³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Human cytochrome P450 4A11 (CYP4A11) plays a role in the regulation of blood pressure through the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE). We therefore investigated the association between a CYP4A11 polymorphism (rs9333025) with hypertension in the Mongolian and Han ethnic groups. We studied 514 Mongolians in a pastoral area, including 201 hypertension patients and 313 normotensive controls, and 524 Han individuals in an urban area, including 215 hypertension patients and 309 normotensive controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Genotype, allele, and dominant inheritance differed significantly between the Mongolian and Han populations (P = 0.006, P = 0.002, and P = 0.003, respectively). Significant differences were also observed in these factors when considering only males (P = 0.001, P = 0.003, and P = 0.001, respectively). For the Han population, recessive inheritance differed significantly between hypertension patients and controls and between male patients and controls (P = 0.005 and P = 0.049, respectively). The genotypic, allelic, and dominant frequencies differed significantly between hypertension patients in both populations (P = 0.019, P = 0.035, and P = 0.024, respectively). The genotypic frequency in Mongolian male patients was significantly different from that in Han male patients (P = 0.009). Higher body mass index, triglycerides, and lower high-density lipoprotein were associated with increased risk of developing hypertension in the Han population. The GG genotype was in higher frequency in the Mongolian population, indicating that it is a high risk factor for hypertension. Mongolian men were at higher risk of developing hypertension.

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Section: Discussionmentioning

confidence: 99%

Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China

Liang¹,

Yan²,

Suyila³

et al. 2014

Genet. Mol. Res.

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“…Many studies have attempted to develop an accurate warfarin dosing algorithm using multiple genes, such as CYP2C9 , VKORC1 , and CYP4F2 [151,152,153,154,155]. Studies regarding CYP4A22 genetic polymorphisms have been limited to certain populations, such as Japanese and French populations [25,156]. The association of CYP4A22 variants with human diseases has still not been investigated, which might be due to low expression levels of the CYP4A22 gene.…”

Section: Genetic Variants Of the Cyp4 Familymentioning

confidence: 99%

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Jarrar

Lee

2019

IJMS

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Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.

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“…Over the past few years, several in silico approaches have been developed particularly for screening functional SNPs and detecting the effect of deleterious nsSNPs in the candidate protein. Many tools can also predict the structural changes based on single amino acid substitution in the protein 24,25 . Based on in silico algorithms, the functional SNPs in BRAF (B-Raf proto-oncogene), BRCA1(Breast cancer type 1 susceptibility protein) 26 , and ATM (Ataxia-Telangiectasia Mutated) genes 27 have been classified successfully from a wide range of disease susceptible SNPs based on their functional and structural consequences.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation

Islam

Khan

Parves

et al. 2019

Sci Rep

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Serine-threonine kinase11 (STK11) is a tumor suppressor gene which plays a key role in regulating cell growth and apoptosis. It is widely known as a multitasking kinase and engaged in cell polarity, cell cycle arrest, chromatin remodeling, energy metabolism, and Wnt signaling. The substitutions of single amino acids in highly conserved regions of the STK11 protein are associated with Peutz–Jeghers syndrome (PJS), which is an autosomal dominant inherited disorder. The abnormal function of the STK11 protein is still not well understood. In this study, we classified disease susceptible single nucleotide polymorphisms (SNPs) in STK11 by using different computational algorithms. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking and molecular dynamics analysis. Our results show that W239R and W308C variants are likely to be highly deleterious mutations found in the catalytic kinase domain, which may destabilize structure and disrupt the activation of the STK11 protein as well as reduce its catalytic efficiency. The W239R mutant is likely to have a greater impact on destabilizing the protein structure compared to the W308C mutant. In conclusion, these mutants can help to further realize the large pool of disease susceptibilities linked with catalytic kinase domain activation of STK11 and assist to develop an effective drug for associated diseases.

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Genetic polymorphism of CYP4A11 and CYP4A22 genes and in silico insights from comparative 3D modelling in a French population

Cited by 16 publications

References 39 publications

Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China

Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation

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