Ioannis P Kosmas1, Athina Tatsioni, John P A Ioannidis. 1. Clinical and Molecular Epidemiology Unit and Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Abstract
OBJECTIVE: To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy. DESIGN: Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677T MTHFR polymorphism. METHODS: Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias. RESULTS: Across 23 comparisons (3169 hypertensive women, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01-1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertension > or = 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03-1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61-1.65). Early published studies tended to show stronger associations than the subsequent studies. CONCLUSIONS: While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.
OBJECTIVE: To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy. DESIGN: Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677TMTHFR polymorphism. METHODS: Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias. RESULTS: Across 23 comparisons (3169 hypertensivewomen, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01-1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertension > or = 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03-1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61-1.65). Early published studies tended to show stronger associations than the subsequent studies. CONCLUSIONS: While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.
Authors: Elias Zintzaras; Georgios Kitsios; Gavan A Harrison; Hannele Laivuori; Katja Kivinen; Juha Kere; Ioannis Messinis; Ioannis Stefanidis; John P A Ioannidis Journal: Hum Genet Date: 2006-07-26 Impact factor: 4.132
Authors: Priyanka Nandakumar; Dongwon Lee; Thomas J Hoffmann; Georg B Ehret; Dan Arking; Dilrini Ranatunga; Man Li; Megan L Grove; Eric Boerwinkle; Catherine Schaefer; Pui-Yan Kwok; Carlos Iribarren; Neil Risch; Aravinda Chakravarti Journal: Hum Mol Genet Date: 2020-07-21 Impact factor: 6.150
Authors: John Allotey; Kym Ie Snell; Melanie Smuk; Richard Hooper; Claire L Chan; Asif Ahmed; Lucy C Chappell; Peter von Dadelszen; Julie Dodds; Marcus Green; Louise Kenny; Asma Khalil; Khalid S Khan; Ben W Mol; Jenny Myers; Lucilla Poston; Basky Thilaganathan; Anne C Staff; Gordon Cs Smith; Wessel Ganzevoort; Hannele Laivuori; Anthony O Odibo; Javier A Ramírez; John Kingdom; George Daskalakis; Diane Farrar; Ahmet A Baschat; Paul T Seed; Federico Prefumo; Fabricio da Silva Costa; Henk Groen; Francois Audibert; Jacques Masse; Ragnhild B Skråstad; Kjell Å Salvesen; Camilla Haavaldsen; Chie Nagata; Alice R Rumbold; Seppo Heinonen; Lisa M Askie; Luc Jm Smits; Christina A Vinter; Per M Magnus; Kajantie Eero; Pia M Villa; Anne K Jenum; Louise B Andersen; Jane E Norman; Akihide Ohkuchi; Anne Eskild; Sohinee Bhattacharya; Fionnuala M McAuliffe; Alberto Galindo; Ignacio Herraiz; Lionel Carbillon; Kerstin Klipstein-Grobusch; SeonAe Yeo; Helena J Teede; Joyce L Browne; Karel Gm Moons; Richard D Riley; Shakila Thangaratinam Journal: Health Technol Assess Date: 2020-12 Impact factor: 4.014