دورية أكاديمية
أعرض في EDS

22q11.2 microdeletion and increased risk for type 2 diabetes.

التفاصيل البيبلوغرافية
العنوان: 22q11.2 microdeletion and increased risk for type 2 diabetes.
المؤلفون: Van L; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Heung T; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; The Dalglish Family 22q Clinic, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada., Malecki SL; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Fenn C; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Tyrer A; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Sanches M; Biostatistical Consulting Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada., Chow EWC; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Boot E; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; The Dalglish Family 22q Clinic, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Advisium, 's Heeren Loo Zorggroep, Amersfoort, the Netherlands., Corral M; The Dalglish Family 22q Clinic, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada., Dash S; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Banting & Best Diabetes Center, University of Toronto, Toronto, Ontario, Canada.; Division of Endocrinology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada., George SR; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Division of Endocrinology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada., Bassett AS; Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.; The Dalglish Family 22q Clinic, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Toronto Congenital Cardiac Centre for Adults, and Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.; Toronto General Research Institute and Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada.
المصدر: EClinicalMedicine [EClinicalMedicine] 2020 Sep 10; Vol. 26, pp. 100528. Date of Electronic Publication: 2020 Sep 10 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: The Lancet Country of Publication: England NLM ID: 101733727 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-5370 (Electronic) Linking ISSN: 25895370 NLM ISO Abbreviation: EClinicalMedicine Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : The Lancet, [2018]-
مستخلص: Background: The 22q11.2 microdeletion is the pathogenic copy number variation (CNV) associated with 22q11.2 deletion syndrome (22q11.2DS, formerly known as DiGeorge syndrome). Familiar endocrinological manifestations include hypoparathyroidism and hypothyroidism, with recent elucidation of elevated risk for obesity in adults. In this study, we aimed to determine whether adults with 22q11.2DS have an increased risk of developing type 2 diabetes (T2D).
Methods: We studied the effect of the 22q11.2 microdeletion on risk for T2D, defined by history and glycosylated hemoglobin (HbA1c), using weighted survey data from the adult Canadian population (based on n  = 11,874) and from a clinical cohort of adults with 22q11.2DS ( n  = 314), aged 17-69 years. Binomial logistic regression models accounted for age, sex, non-European ethnicity, family history of T2D, obesity, and antipsychotic medication use.
Findings: The 22q11.2 microdeletion was a significant independent risk factor for T2D (OR 2·44, 95% CI 1·39-4·31), accounting for other factors ( p < 0·0001). All factors except sex were also significant within 22q11.2DS. The median age at diagnosis of T2D was significantly younger in 22q11.2DS than in the Canadian population sample (32 vs 50 years, p  < 0·0001). In adults without T2D, HbA1c was significantly higher in 22q11.2DS than the population ( p  = 0·042), after accounting for younger age of the 22q11.2DS group.
Interpretation: The results support the 22q11.2 microdeletion as a novel independent risk factor and potential model for early onset T2D. The findings complement emerging evidence that rare CNVs may contribute to risk for T2D. The results have implications for precision medicine and research into the underlying pathogenesis of T2D.
Competing Interests: The authors have declared no conflicts of interest.
(© 2020 The Authors.)
References: Can J Diabetes. 2018 Apr;42 Suppl 1:S16-S19. (PMID: 29650090)
Genet Med. 2017 Feb;19(2):204-208. (PMID: 27537705)
Am J Hum Genet. 2007 Nov;81(5):1057-69. (PMID: 17924346)
Diabetes Metab Syndr Obes. 2019 Jul 08;12:1047-1056. (PMID: 31360071)
Lancet. 2017 Jun 3;389(10085):2239-2251. (PMID: 28190580)
Genet Med. 2015 Aug;17(8):599-609. (PMID: 25569435)
J Med Genet. 2019 Mar;56(3):131-138. (PMID: 30343275)
Mol Psychiatry. 2021 Aug;26(8):4496-4510. (PMID: 32015465)
Lancet Diabetes Endocrinol. 2018 Nov;6(11):891-900. (PMID: 29699867)
N Engl J Med. 2017 Feb 23;376(8):742-754. (PMID: 28121514)
Am J Med Genet A. 2018 Apr;176(4):936-944. (PMID: 29575622)
Transl Psychiatry. 2018 Nov 23;8(1):252. (PMID: 30470734)
Lancet Diabetes Endocrinol. 2018 Jan;6(1):69-80. (PMID: 28847479)
Can J Diabetes. 2018 Apr;42 Suppl 1:S10-S15. (PMID: 29650080)
JAMA Neurol. 2013 Nov;70(11):1359-66. (PMID: 24018986)
Sci Rep. 2017 Dec 6;7(1):17105. (PMID: 29213072)
Genet Med. 2020 Jan;22(1):132-141. (PMID: 31363180)
Nat Rev Dis Primers. 2015 Nov 19;1:15071. (PMID: 27189754)
Nat Genet. 2008 Jun;40(6):751-60. (PMID: 18469815)
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3428-3436. (PMID: 30912798)
J Neurodev Disord. 2015;7(1):18. (PMID: 26137170)
Diabetes Care. 2008 Oct;31(10):1991-6. (PMID: 18628569)
Neuropsychopharmacology. 2010 Aug;35(9):1997-2004. (PMID: 20520598)
N Engl J Med. 2010 Mar 4;362(9):800-11. (PMID: 20200384)
Genet Med. 2019 Oct;21(10):2328-2335. (PMID: 30948858)
Diabetes Care. 2019 Jan;42(Suppl 1):S13-S28. (PMID: 30559228)
Sci Rep. 2015 Sep 09;5:13871. (PMID: 26350756)
فهرسة مساهمة: Keywords: Diabetes; Early diagnosis; Genetics; Genotype; Molecular diagnostics; Risk; Structural variant
تواريخ الأحداث: Date Created: 20201022 Latest Revision: 20240329
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7565196
DOI: 10.1016/j.eclinm.2020.100528
PMID: 33089125
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-5370
DOI:10.1016/j.eclinm.2020.100528