A common <i>ABCC2</i> promoter polymorphism is not a determinant of the risk of spina bifida

Jensen, Liselotte E.; Wall, Amelia M.; Cook, Michelle; Hoess, Katy; Thorn, Caroline F.; Whitehead, Alexander S.; Mitchell, Laura E.

doi:10.1002/bdra.20023

Cited by 9 publications

(5 citation statements)

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“…Data from subsets of the families enrolled in Phase 1 of the SBRR have been used to evaluate the association between spina bifida and several putative candidate genes: MTR and MTRR (Doolin et al, 2002), NOS3 (Brown et al, 2004), T (Jensen et al, 2004a), ABCC2 (Jensen et al, 2004b), and NAT1 (Jensen et al, 2005, 2006), and additional candidate gene studies based on the full Phase 1 group are forthcoming. The information contained in the present article will provide a useful supplement to the publications describing these studies, because it includes a more comprehensive description of the study design and participants than a typical Material and Methods section.…”

Section: Discussionmentioning

confidence: 99%

Spina Bifida Research Resource: Study design and participant characteristics

Mitchell

2008

Birth Defects Research

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Section: Discussionmentioning

confidence: 99%

Spina Bifida Research Resource: Study design and participant characteristics

Mitchell

2008

Birth Defects Research

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“…Diclofenac is labeled with four different ATC codes (i.e., four different therapeutic uses) and associated with a number of targets categorized by DrugBank, including prostaglandin G/H synthase 1 and 2, the cytochrome P450 family (2C18/2E1/2C19/1A2/2C8/2D6/2C9/3A4/1A1/2B6), the UDP-glucuronosyltransferase family (1–1,2B7), prostaglandin G/H synthase 1, etc. Several case-control studies have been carried out to investigate the role of polymorphisms in the gene encoding regions of the aforementioned drug-metabolizing enzymes and transporters to determine susceptibility to diclofenac-induced hepatotoxicity [26] , [27] , [28] , [29] , [30] . Diclofenac has been withdrawn in several countries due to liver injury and other adverse drug reactions, including ulcers, bleeding, and ulcerations in the stomach and intestinal linings [31] .…”

Section: Discussionmentioning

confidence: 99%

Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

et al. 2011

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Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

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“…Briefly, log-linear analysis has been widely used in genetic association studies of birth defects (e.g. [32], [33], [34], [35], [36]), and involves comparing the observed distribution of genotypes in the triads to the expected genotypes under the assumptions of both Mendelian inheritance and symmetry of maternal and parental genotypes [28], [29], [30]. Log-linear analysis has the advantage over the transmission disequilibrium test (TDT) of allowing for the evaluation of maternal as well as inherited genetic effects [28], [29], [30].…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Association Study of Maternal and Inherited Loci for Conotruncal Heart Defects

et al. 2014

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Conotruncal and related heart defects (CTDs) are a group of serious and relatively common birth defects. Although both maternal and inherited genotypes are thought to play a role in the etiology of CTDs, few specific genetic risk factors have been identified. To determine whether common variants acting through the genotype of the mother (e.g. via an in utero effect) or the case are associated with CTDs, we conducted a genome-wide association study of 750 CTD case-parent triads, with follow-up analyses in 358 independent triads. Log-linear analyses were used to assess the association of CTDs with the genotypes of both the mother and case. No association achieved genomewide significance in either the discovery or combined (discovery+follow-up) samples. However, three loci with p-values suggestive of association (p<10−5) in the discovery sample had p-values <0.05 in the follow-up sample and p-values in the combined data that were lower than in the discovery sample. These included suggestive association with an inherited intergenic variant at 20p12.3 (rs6140038, combined p = 1.0×10−5) and an inherited intronic variant in KCNJ4 at 22q13.1 (rs2267386, combined p = 9.8×10−6), as well as with a maternal variant in SLC22A24 at 11q12.3 (rs11231379, combined p = 4.2×10−6). These observations suggest novel candidate loci for CTDs, including loci that appear to be associated with the risk of CTDs via the maternal genotype, but further studies are needed to confirm these associations.

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A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida

Abstract: The results of the present analyses suggest that the C(-24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk.

Cited by 9 publications

References 25 publications

Spina Bifida Research Resource: Study design and participant characteristics

Spina Bifida Research Resource: Study design and participant characteristics

Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

Genome-Wide Association Study of Maternal and Inherited Loci for Conotruncal Heart Defects

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