Maternal folate polymorphisms and the etiology of human nondisjunction.
Attempts to identify genetic contributors to human meiotic nondisjunction have met with little, if any, success. Thus, recent reports linking Down syndrome to maternal polymorphisms at either of two folate metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have generated considerable interest. In the present report, we asked whether variation at MTHFR (677C-->T) or MTRR (66A-->G) might be associated with human trisomies other than trisomy 21. We analyzed maternal polymorphisms at MTHFR and MTRR in 93 cases of sex-chromosome trisomy, 44 cases of trisomy 18, and 158 cases of autosomal trisomies 2, 7, 10, 13, 14, 15, 16, 18, or 22, and compared the distributions of genotypes to those of control populations. We observed a significant increase in the MTHFR polymorphism in mothers of trisomy 18 conceptuses but were unable to identify any other significant associations. Overall, our observations suggest that, at least for the sex chromosomes and for a combined set of autosomal trisomies, polymorphisms in the folate pathway are not a significant contributor to human meiotic nondisjunction.
Hassold
T J
TJ
Department of Genetics and The Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA. tjh6@po.cwru.edu
Burrage
L C
LC
Chan
E R
ER
Judis
L M
LM
Schwartz
S
S
James
S J
SJ
Jacobs
P A
PA
Thomas
N S
NS
D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004739:England; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005315:Fetal Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008540:Meiosis / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008969:Molecular Sequence Data; D009630:Nondisjunction, Genetic; D009820:Ohio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D012729:Sex Chromosome Aberrations / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D014314:Trisomy / Q000235:genetics* / Q000503:physiopathology
D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)