Joint analysis of individual participants’ data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index
Cornelia Huth,Thomas Illig,Christian Herder,Christian Gieger,Harald Grallert,Caren Vollmert,Wolfgang Rathmann,Yasmin H. Hamid,Oluf Pedersen,Torben Hansen,Barbara Thorand,Christa Meisinger,Angela Döring,Norman Klopp,Henning Gohlke,Wolfgang Lieb,Christian Hengstenberg,Valeriya Lyssenko,Leif Groop,Helen Ireland,Jeffrey W. Stephens,Ingrid Wernstedt Asterholm,John-Olov Jansson,Heiner Boeing,Matthias Möhlig,Heather M. Stringham,Michael Boehnke,Jaakko Tuomilehto,José Manuel Fernández-Real,Abel López-Bermejo,L. Gallart,Joan Vendrell,Steve E. Humphries,Florian Kronenberg,H.-Erich Wichmann,Iris M. Heid +35 more
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TLDR
The data suggest that C-allele carriers of the IL6 -174G>C polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.Abstract:
Background. Several studies have investigated associations between the -174GC single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results. Aims. This joint analysis aimed to clarify whether IL6 -174GC was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI). Methods. Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P0.1), they were combined by using the inverse-variance fixed-effect model. Results. The main analysis included 9440, 7398, 24,117, or 5659 non-diabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI, or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (-0.091 mmol/L, P=0.014). There was no evidence for association between IL6 -174GC and BMI or interleukin-6 levels, except in some subgroups. Conclusions. Our data suggest that C-allele carriers of the IL6 -174GC polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.read more
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The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.
Daniel I. Swerdlow,Michael V. Holmes,Karoline Kuchenbaecker,Engmann Jel.,Tina Shah,Reecha Sofat,Yiran Guo,C Chung,Anne Peasey,Roman Pfister,Simon P. Mooijaart,Helen Ireland,Maarten Leusink,Claudia Langenberg,KaWah Li,Jutta Palmen,Phil Howard,Jackie A. Cooper,Fotios Drenos,John Hardy,Mike A. Nalls,Yun Li,Gordon D.O. Lowe,Marlene C. W. Stewart,S. J. Bielinski,Julian Peto,Nicholas J. Timpson,John Gallacher,Malcolm G. Dunlop,Richard S. Houlston,Ian Tomlinson,Ioanna Tzoulaki,Jian'an Luan,Boer Jma.,Nita G. Forouhi,N. C. Onland-Moret,Y. T. van der Schouw,Renate B. Schnabel,Jaroslav A. Hubacek,Růžena Kubínová,Migle Baceviciene,Abdonas Tamosiunas,Andrzej Pajak,Roman Topor-Madry,Sofia Malyutina,Damiano Baldassarre,Bengt Sennblad,Elena Tremoli,U de Faire,Luigi Ferrucci,S Bandenelli,Tetsu Tanaka,James F. Meschia,AB Singleton,Gerjan Navis,I. Mateo Leach,Bakker Sjl.,Ron T. Gansevoort,Ian Ford,Stephen E. Epstein,Mary-Susan Burnett,Joe Devaney,Johan Wouter Jukema,Westendorp Rgj.,G Jan de Borst,Y. van der Graaf,P A de Jong,Mailand-van der Zee A-H.,Olaf H. Klungel,A. de Boer,P. A. Doevendans,Jeffrey W. Stephens,Charles B. Eaton,Jennifer G. Robinson,JoAnn E. Manson,F G Fowkes,Timothy M. Frayling,Jenna Price,Peter H. Whincup,Richard W Morris,Debbie A Lawlor,George Davey Smith,Yoav Ben-Shlomo,Susan Redline,Leslie A. Lange,Meena Kumari,Nicholas J. Wareham,Verschuren Wmm.,Emelia J. Benjamin,John C. Whittaker,Anders Hamsten,Frank Dudbridge,Delaney Jac.,Andrew Wong,Diana Kuh,Rebecca Hardy,Berta Almoguera Castillo,John Connolly,P. van der Harst,Eric J. Brunner,Michael Marmot,Christina L. Wassel,Steve E. Humphries,P.J. Talmud,Mika Kivimäki,Folkert W. Asselbergs,Mikhail I. Voevoda,Martin Bobak,Hynek Pikhart,James G. Wilson,Hakon Hakonarson,Alexander P. Reiner,Brendan J. Keating,Naveed Sattar,Aroon D. Hingorani,Juan P. Casas +115 more
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Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.
Giovanni Fiorito,Cathal McCrory,Oliver Robinson,Cristian Carmeli,Carolina Ochoa Rosales,Carolina Ochoa Rosales,Yan Zhang,Elena Colicino,Pierre Antoine Dugué,Fanny Artaud,Gareth J. McKay,Ayoung Jeong,Ayoung Jeong,Pashupati P. Mishra,Therese Haugdahl Nøst,Therese Haugdahl Nøst,Vittorio Krogh,Salvatore Panico,Carlotta Sacerdote,Rosario Tumino,Domenico Palli,Giuseppe Matullo,Simonetta Guarrera,Martina Gandini,Murielle Bochud,Emmanouil Dermitzakis,Taulant Muka,Taulant Muka,Joel Schwartz,Pantel S. Vokonas,Allan C. Just,Allison M. Hodge,Allison M. Hodge,Graham G. Giles,Graham G. Giles,Graham G. Giles,Melissa C. Southey,Melissa C. Southey,Melissa C. Southey,Mikko Hurme,Ian S. Young,Amy Jayne McKnight,Sonja Kunze,Melanie Waldenberger,Annette Peters,Lars Schwettmann,Eiliv Lund,Andrea A. Baccarelli,Roger L. Milne,Rose Anne Kenny,Alexis Elbaz,Hermann Brenner,Hermann Brenner,Frank Kee,Trudy Voortman,Nicole Probst-Hensch,Nicole Probst-Hensch,Terho Lehtimäki,Paul Elliot,Silvia Stringhini,Silvia Stringhini,Paolo Vineis,Silvia Polidoro +62 more
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Associations of IL6 polymorphisms with lung function decline and COPD
Jian Qing He,Marilyn G. Foreman,Karey Shumansky,Xuekui Zhang,Loubna Akhabir,Don D. Sin,Shu Fan Paul Man,Dawn L. DeMeo,Augusto A. Litonjua,Edwin K. Silverman,John E. Connett,N. R. Anthonisen,Robert A. Wise,Peter D. Paré,Andrew J. Sandford +14 more
TL;DR: The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV1 and susceptibility to COPD in smokers.
Journal ArticleDOI
Genetic variants and the metabolic syndrome: a systematic review
TL;DR: For most single nucleotide polymorphisms (SNPs) no systematic review on their association with metabolic syndrome exists as mentioned in this paper. But for most SNPs no systematic literature search was conducted until the 2nd of June 2010, using HuGE Navigator.
References
More filters
Journal ArticleDOI
Bias in meta-analysis detected by a simple, graphical test
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Journal ArticleDOI
Quantifying heterogeneity in a meta‐analysis
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Journal ArticleDOI
Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030
TL;DR: Findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant, and given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
Journal ArticleDOI
The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.
TL;DR: There is a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals, and the reduced frequency of the potentially protective CC genotype in young S-JCA patients may contribute to its pathogenesis.
Journal ArticleDOI
Interleukin-6-deficient mice develop mature-onset obesity.
Ville Wallenius,Kristina Wallenius,Bo Ahrén,Mats Rudling,Hans Carlsten,Suzanne L. Dickson,Claes Ohlsson,John-Olov Jansson +7 more
TL;DR: In this article, the authors investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding interleukin-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-six replacement.