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dc.contributor.authorUrbanek, Men
dc.contributor.authorHayes, MGen
dc.contributor.authorLee, Hen
dc.contributor.authorFreathy, RMen
dc.contributor.authorLowe, LPen
dc.contributor.authorAckerman, Cen
dc.contributor.authorJafari, Nen
dc.contributor.authorDyer, ARen
dc.contributor.authorCox, NJen
dc.contributor.authorDunger, Daviden
dc.contributor.authorHattersley, ATen
dc.contributor.authorMetzger, BEen
dc.contributor.authorLowe, WLen
dc.date.accessioned2017-04-04T13:31:03Z
dc.date.available2017-04-04T13:31:03Z
dc.date.issued2012-03-30en
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263462
dc.description.abstractBACKGROUND: Since mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome. RESULTS: Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value = 4.4×10(-5)), RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1×10(-4)), IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3×10(-4)), ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value = 1.4×10(-4)), LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value = 2.4×10(-4)), and IL6 and 1-hour plasma glucose (rs6954897; -2.29 mg/dl decrease per allele G, p-value = 4.3×10(-4)). CONCLUSIONS: Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha,) may contribute to metabolic phenotypes in pregnant women.
dc.description.sponsorshipThe study is funded by grants R01 DK067459, R01-HD34242 and R01-HD34243 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes, Digestive, and Kidney Diseases, by the National Center for Research Resources (M01-RR00048, M01-RR00080), and by the American Diabetes Association. RMF is funded by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant: 085541/Z/08/Z). ATH is employed as a core member of the Peninsula NIHR Clinical Research Facility. Support has also been provided to local field centers by Diabetes UK (RD04/0002756), Kaiser Permanente Medical Center, KK Women's and Children's Hospital, Mater Mother's Hospital, Novo Nordisk, the Myre Sim Fund of the Royal College of Physicians of Edinburgh, and the Howard and Carol Bernick Family Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.languageengen
dc.language.isoenen
dc.publisherPLoS
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAsian Continental Ancestry Groupen
dc.subjectBlood Glucoseen
dc.subjectC-Peptideen
dc.subjectCohort Studiesen
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectFastingen
dc.subjectFemaleen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGlucose Tolerance Testen
dc.subjectHemoglobin A, Glycosylateden
dc.subjectHumansen
dc.subjectHyperglycemiaen
dc.subjectInflammationen
dc.subjectInterleukin-6en
dc.subjectInterleukin-8en
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectPregnancyen
dc.subjectPregnancy Complicationsen
dc.subjectPregnancy Outcomeen
dc.subjectReceptors, Adiponectinen
dc.subjectReceptors, Leptinen
dc.subjectResistinen
dc.subjectSignal Transductionen
dc.subjectThailanden
dc.subjectTumor Necrosis Factor-alphaen
dc.titleThe role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancyen
dc.typeArticle
prism.endingPagee32958
prism.issueIdentifier3en
prism.publicationDate2012en
prism.publicationNamePLoS Oneen
prism.startingPagee32958
prism.volume7en
dc.identifier.doi10.17863/CAM.8807
dcterms.dateAccepted2012-02-08en
rioxxterms.versionofrecord10.1371/journal.pone.0032958en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2012-03-30en
dc.contributor.orcidDunger, David [0000-0002-2566-9304]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Reviewen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International