Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

Nakamoto, Kaori; Wang, Shuang; Jenison, Robert; Guo, Grace L.; Klaassen, Curtis D.; Wan, Yu‐Jui Yvonne; Zhong, Xiao Bo

doi:10.1186/1471-2156-7-29

Cited by 30 publications

(10 citation statements)

References 34 publications

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“…Genetic variants of the CYP7A1 gene have been studied in human populations [70]. CYP7A1 genetic variants have been associated with defects in cholesterol and bile acid homeostasis [71].…”

Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 99%

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Bao

Rasmussen

et al. 2018

Curr Pharmacol Rep

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Purpose of this Review In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors. The purpose of this review is to provide information on genetic variations associated with isoniazid- and rifampicin-mediated AT-DILI. Recent Findings The genetic variations associated with AT-DILI have been identified in the genomic regions within or near genes encoding proteins in the following pathways: drug metabolizing enzymes (NAT2, CYP2E1, and GSTs), accumulation of bile acids, lipids, and heme metabolites (CYP7A1, BSEP, UGTs, and PXR), immune adaptation (HLAs and TNF-α), and oxidant challenge (TXNRD1, SOD1, BACH1, and MAFK). Summary The information summarized in this review considers the genetic bases of risk factors contributing to AT-DILI and provides information that may help for future studies. Some of the implicated genetic variations can be used in the design of genetic tests and serve as biomarkers for the prediction of isoniazid- and rifampicin-mediated AT-DILI risk in personalized medicine.

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“…Genetic variants of the CYP7A1 gene have been studied in human populations [70]. CYP7A1 genetic variants have been associated with defects in cholesterol and bile acid homeostasis [71].…”

Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 99%

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Bao

Rasmussen

et al. 2018

Curr Pharmacol Rep

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“…Additionally, GLP-1 may improve insulin sensitivity in patients with type 2 diabetes and animal models [35]. CYP7A1 is the rate-limiting enzyme of the bile acid (BA) synthesis pathway, which is the pivotal mechanism for maintaining the balance between cholesterol and BA [36]. HMGCR is a key enzyme in the metabolism of glycolipids in the body and has been recognized as an important target for hypolipidemic drugs (statins).…”

Section: Discussionmentioning

confidence: 99%

Chitooligosaccharides Modulate Glucose-Lipid Metabolism by Suppressing SMYD3 Pathways and Regulating Gut Microflora

et al. 2020

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Chitooligosaccharides (COS) have a variety of biological activities due to their positively charged amino groups. Studies have shown that COS have antidiabetic effects, but their molecular mechanism has not been fully elucidated. The present study confirmed that COS can reduce hyperglycemia and hyperlipidemia, prevent obesity, and enhance histological changes in the livers of mice with type 2 diabetes mellitus (T2DM). Additionally, treatment with COS can modulate the composition of the gut microbiota in the colon by altering the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. Furthermore, in T2DM mice, treatment with COS can upregulate the cholesterol-degrading enzymes cholesterol 7-alpha-hydroxylase (CYP7A1) and incretin glucagon-like peptide 1 (GLP-1) while specifically inhibiting the transcription and expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the key enzyme in cholesterol synthesis. Furthermore, using an oleic acid-induced hepatocyte steatosis model, we found that HMGCR can be directly transactivated by SET and MYND domain containing 3 (SMYD3), a transcriptional regulator, via 5′-CCCTCC-3′ element in the promoter. Overexpression of SMYD3 can suppress the inhibitory effect of COS on HMGCR, and COS might regulate HMGCR by inhibiting SMYD3, thereby exerting hypolipidemic functions. To the best of our knowledge, this study is the first to illustrate that COS mediate glucose and lipid metabolism disorders by regulating gut microbiota and SMYD3-mediated signaling pathways.

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“…The m204T>G is located in a region of conserved sequence containing several transcription factor binding motifs for PPARs and hepatocyte nuclear factor-4 (HNF4) [24] and represents the haplotype block covering a substantial part of the promoter and the first exon of this gene [25]. In vitro studies have indicated that PPARα and fibrate reduce the availability of HNF-4 for binding to the response sequence or competing with HNF-4 for the same binding site and therefore attenuate the transactivation of CYP7A1 by HNF-4 [24, 26].…”

Section: Discussionmentioning

confidence: 99%

“…However, the major allele of this variant displayed less responsiveness to fenofibrate-induce HDL–C increases compared with the minor allele. The differential modulation of these two variants on fenofibrate responses may stem from independent mechanisms which the two variants mediate as both variants are identified as tagging SNPs [25] with limited correlation and each representing an independent haplotype in a White population.…”

Section: Discussionmentioning

confidence: 99%

The Effect of CYP7A1 Polymorphisms on Lipid Responses to Fenofibrate

Shen

Arnett

Parnell

et al. 2012

Journal of Cardiovascular Pharmacology

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CYP7A1 encodes cholesterol 7α-hydroxylase an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is down-regulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate. We examined associations of three tagging single nuclear polymorphisms (SNP) (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and HDL-C responses to a 3-week treatment with fenofibrate 160 mg/d in 864 US White participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. The m204T>G variant significantly associated TG and HDL-C responses to fenofibrate. Individual homozygous for the common T allele of m204T>G SNP displayed both the greater reduction of TG (−32% for TT, −28% for GT, −25% for GG, P = 0.004) and an increase of HDL-C response compared to non-carriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed greater increase of HDL-C response compared to non-carriers (2.8% CC, 4.5% for CT, 5.8% for TT, P=0.02) albeit no significant effect on TG response. Our data suggest that common variants at CYP7A1 locus modulate the TG lowering and HDL-C raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses.

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Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

Cited by 30 publications

References 34 publications

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Chitooligosaccharides Modulate Glucose-Lipid Metabolism by Suppressing SMYD3 Pathways and Regulating Gut Microflora

The Effect of CYP7A1 Polymorphisms on Lipid Responses to Fenofibrate

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