Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide
Top Cited Papers
Open Access
- 1 August 2003
- journal article
- research article
- Published by BMJ in Journal of Medical Genetics
- Vol. 40 (8), 619-625
- https://doi.org/10.1136/jmg.40.8.619
Abstract
Since its biochemical characterisation in 19911 and its genetic identification in 1995,2 677C>T allele (T allele) of the 5,10 methylenetetrahydrofolate reductase ( MTHFR ) gene has been a focus of increasing interest from researchers world wide. The expanding spectrum of common conditions linked with the 677C>T allele now includes certain adverse birth outcomes (including birth defects), pregnancy complications, cancers, adult cardiovascular diseases, and psychiatric disorders.3–8 Although several of these associations remain unconfirmed or controversial,4 their scope is such that it becomes of interest to explore the geographical and ethnic distribution of the allele and associated genotypes.9 Accurate information on such distribution can contribute to studies of gene-disease associations (by providing reference population data) and population genetics (by highlighting geographical and ethnic variations suggestive of evolutionary pressures),10 as well as help to evaluate health impact (by allowing estimates of population attributable fraction). Current population data, however, show gaps and even for some ethnic groups or large geographical areas (for example, China) few data are available.3 Our aim was to supplement the available data by collecting a large and diverse sample of newborns from different geographical areas and ethnic groups, and to examine international variations in the distribution of the 677C>T allele. We present findings relating to more than 7000 newborns from 16 areas around the world. The study was conducted under the auspices of the International Clearinghouse for Birth Defect Monitoring Systems (ICBDMS) and was coordinated through its head office, the International Center on Birth Defects (ICBD). ### Sample selection Participating programmes, in consultation with the coordinating group, identified a population sampling approach that would be simple yet minimise sampling bias with respect to the MTHFR genotype. We made an explicit attempt to sample systematically the newborn population. Details of each programme’s approach are listed below, and further …Keywords
This publication has 18 references indexed in Scilit:
- Absence of Association of Thrombophilia Polymorphisms with Intrauterine Growth RestrictionThe New England Journal of Medicine, 2002
- The Frequent 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphism Is Associated with a Common Haplotype in Whites, Japanese, and AfricansAmerican Journal of Human Genetics, 2002
- MTRR and MTHFR polymorphism: Link to Down syndrome?American Journal of Medical Genetics, 2001
- Maternal Folate Polymorphisms and the Etiology of Human NondisjunctionAmerican Journal of Human Genetics, 2001
- Polymorphisms in Genes Involved in Folate Metabolism as Maternal Risk Factors for Down SyndromeAmerican Journal of Human Genetics, 2000
- High Prevalence of the Thermolabile Methylenetetrahydrofolate Reductase Variant in Mexico: A Country with a Very High Prevalence of Neural Tube DefectsMolecular Genetics and Metabolism, 1999
- Folic Acid and Homocyst(e)ine Metabolic Defects and the Risk of Placental Abruption, Pre-eclampsia and Spontaneous Pregnancy Loss: A Systematic ReviewPlacenta, 1999
- The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.Journal of Medical Genetics, 1998
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995
- Confidence intervals for a binomial proportionStatistics in Medicine, 1993