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dc.contributor.authorHjort, Rebecka
dc.contributor.authorLöfvenborg, Josefin E.
dc.contributor.authorAhlqvist, Emma
dc.contributor.authorAlfredsson, Lars
dc.contributor.authorAndersson, Tomas
dc.contributor.authorGrill, Valdemar Erik Robert
dc.contributor.authorGroop, Leif
dc.contributor.authorSørgjerd, Elin Pettersen
dc.contributor.authorTuomi, Tiinamaija
dc.contributor.authorÅsvold, Bjørn Olav
dc.contributor.authorCarlsson, Sofia
dc.date.accessioned2021-09-20T07:23:22Z
dc.date.available2021-09-20T07:23:22Z
dc.date.created2020-01-09T09:02:53Z
dc.date.issued2019
dc.identifier.citationJournal of Clinical Endocrinology and Metabolism. 2019, 104 (10), 4815-4826.en_US
dc.identifier.issn0021-972X
dc.identifier.urihttps://hdl.handle.net/11250/2779013
dc.description.abstractObjective We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Methods We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). Results The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. Conclusions Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.titleInteraction between overweight and genotypes of HLA, TCF7L2, and FTO in relation to the risk of latent autoimmune diabetes in adults and type 2 diabetesen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber4815-4826en_US
dc.source.volume104en_US
dc.source.journalJournal of Clinical Endocrinology and Metabolismen_US
dc.source.issue10en_US
dc.identifier.doi10.1210/jc.2019-00183
dc.identifier.cristin1768976
dc.description.localcodeThis version of the article will not be available due to copyright restrictions (c) 2019 by Oxforden_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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