Maternal homocysteine in pregnancy and offspring birthweight: epidemiological associations and Mendelian randomization analysis.

Autor:	Yajnik CS; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK diabetes@kemdiabetes.org chandakgrc@ccmb.res.in., Chandak GR; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK diabetes@kemdiabetes.org chandakgrc@ccmb.res.in., Joglekar C; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Katre P; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Bhat DS; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Singh SN; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Janipalli CS; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Refsum H; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Krishnaveni G; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Veena S; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Osmond C; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Fall CH; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India, Adjunct Group Leader, Adjunct Group, Genome Institute of Singapore, Singapore, Persistent Systems Ltd, Pune, India, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Pharmacology, University of Oxford, Oxford, UK, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India and MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Jazyk:	angličtina
Zdroj:	International journal of epidemiology [Int J Epidemiol] 2014 Oct; Vol. 43 (5), pp. 1487-97. Date of Electronic Publication: 2014 Jul 22.
DOI:	10.1093/ije/dyu132
Abstrakt:	Background: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. Methods: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C→T) by instrumental variable and triangulation analysis, separately and using meta-analysis. Results: Median (IQR) homocysteine concentration and mean (SD) birthweight were 8.6 µmol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0 µmol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight was inversely related to maternal homocysteine concentration-PMNS: -22 g/SD [95% confidence interval (CI): (-50, 5), adjusted for gestational age and offspring gender]; Parthenon: -57 g (-92, -21); meta-analysis: -40 g (-62, -17)]. Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS: 0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26 SD (0.14, 0.39)]; and lower birthweight [PMNS: -46 g (-102, 11, adjusted for gestational age, offspring gender and rs1801133 genotype); Parthenon: -78 g (-170, 15); meta-analysis: -61 g (-111, -10)]. Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight. Conclusions: Our findings suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth. Reducing maternal homocysteine concentrations may improve fetal growth. (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Databáze:	MEDLINE
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