Variants of the human <i>NR1I2</i> (<i>PXR</i>) locus in chronic periodontitis

Folwaczny, Matthias; Tengler, Barbara; Glas, Jürgen

doi:10.1111/j.1600-0765.2011.01417.x

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…However, there are also some deficiencies in our study. For instance, we paid more attention to the NR1I2 variants, which had the functions reported in vitro or in vivo such as -25385C>T, -24113G>A, -24020[GAGAAG]/(-), 7635A>G, and 8055C>T [18], [19], [20], [42], [49], [50], [56]–[58]. The rarely reported or less concerned NR1I2 variants were not included in this research.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

Gao

Tang

et al. 2013

PLoS ONE

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This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value<0.05). AUC ratio and AUC_hyd of NR1I2 -24113AA variant were markedly lower than GA and GG genotypes (7.5±2.1 versus 14.5±3.3 and 20.6±1.1, and 8873±1431 versus 14,504±2218 and 17,586±1046) in the induced states. However, -24020(-)/(-) variant didn't show significant difference in the induction of CYP2B6 hydroxylation activity by SF compared with other -24020[GAGAAG]/(-) genotypes. NR1I2 TGT haplotype (-25385T+g.7635G+g.8055T) carriers exhibited a significantly decreased AUC ratio, compared with TGT noncarriers, in the basal states (7.6±1.0 versus 9.7±1.0), while this result wasn't observed in CYP2B6*6 noncarriers. Moreover, individuals with complete mutation-type [CYP2B6*6/*6+NR1I2 TGT+ -24113AA+ -24020 (-)/(-)] showed even lower percent difference of AUC ratio (8.7±1.2 versus 39.5±8.2) than those with complete wild-type. In conclusion, it is suggested that NR1I2 variants decrease the bupropion hydroxylation induced by SF treatment, particularly in CYP2B6*6 carriers.Trial RegistrationChiCTR.org ChiCTR-TRC-11001285

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Section: Discussionmentioning

confidence: 99%

Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

Gao

Tang

et al. 2013

PLoS ONE

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Relationship between NR1I2 polymorphisms and inflammatory bowel disease risk: A systematic review and meta-analysis

Sun

Lin

2017

Clinics and Research in Hepatology and Gastroenterology

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Host genetics role in the pathogenesis of periodontal disease and caries

Nibali

Iorio

et al. 2017

J Clinic Periodontology

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Background: This study aimed to produce the latest summary of the evidence for association of host genetic variants contributing to both periodontal diseases and caries. Materials and Methods: Two systematic searches of the literature were conducted in Ovid Medline, Embase, LILACS and Cochrane Library for large candidate gene studies (CGS), systematic reviews and genome-wide association studies reporting data on host genetic variants and presence of periodontal disease and caries. Results: A total of 124 studies were included in the review (59 for the periodontitis outcome and 65 for the caries outcome), from an initial search of 15,487 titles. Gene variants associated with periodontitis were categorized based on strength of evidence and then compared with gene variants associated with caries. Several gene variants showed moderate to strong evidence of association with periodontitis, although none of them had also been associated with the caries trait. Conclusions: Despite some potential aetiopathogenic similarities between periodontitis and caries, no genetic variants to date have clearly been associated with both diseases. Further studies or comparisons across studies with large sample size and clear phenotype definition could shed light into possible shared genetic risk factors for caries and periodontitis. Inflammatory periodontal diseases and caries are the most common bacteria-mediated diseases of mankind despite being highly preventable. Periodontal diseases are characterized by an inflammatory reaction against members of the oral microbiota (Curtis 2015) and, among them, Periodontitis (PD) leads to apical migration of the epithelial attachment and resorption of connective tissue and alveolar bone, often resulting in early tooth loss. Heritability has long been thought to play an important role in the predisposition to periodontitis (Baer 1971). Genetic factors are now thought to determine about half the variance of periodontitis risk in the population (Michalowicz et al. 1991). Common single-nucleotide polymorphisms (SNPs) able to affect gene activity or protein production, with an effect on structural factors of the periodontium or on the host response to microbial challenge, are among possible risk factors for periodontitis. LuigiHowever, despite research dating back nearly two decades (Kornman et al. 1997), no single gene variant has yet clearly emerged as definitely predisposing to periodontitis.Caries leads to continued localized mineral loss from the dental enamel and as it progresses, subclinical mineral losses become visible (white spot lesions) and eventually unsupported enamel collapses (cavities) (Vieira 2016). Caries is traditionally described as the interplay among a susceptible host, microbiota and diet (Keyes 1960 (Hunt et al. 1944). Depending on the surrogate measure of the disease employed, genetics explain 25-64% of the variance of the disease seen in the population (reviewed in Vieira et al. 2014).Since both periodontitis and caries are bacteria-mediated oral diseases and depen...

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Variants of the human NR1I2 (PXR) locus in chronic periodontitis

Abstract: A rare haplotype of the NR1I2 (PXR) locus was associated with the individual susceptibility for chronic periodontitis in a German cohort. As a result of the borderline significance and the small effect size the present results need further confirmation.

Cited by 4 publications

References 29 publications

Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

Relationship between NR1I2 polymorphisms and inflammatory bowel disease risk: A systematic review and meta-analysis

Host genetics role in the pathogenesis of periodontal disease and caries

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