Hassold T J, Burrage L C, Chan E R, Judis L M, Schwartz S, James S J, Jacobs P A, Thomas N S
Department of Genetics and The Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Am J Hum Genet. 2001 Aug;69(2):434-9. doi: 10.1086/321971. Epub 2001 Jul 5.
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.
试图确定导致人类减数分裂不分离的基因因素，即便有过尝试，也收效甚微。因此，近期有报告称，唐氏综合征与两种叶酸代谢酶——亚甲基四氢叶酸还原酶（MTHFR）和甲硫氨酸合成酶还原酶（MTRR）中的任何一种的母体多态性有关，这引发了相当大的关注。在本报告中，我们探讨了MTHFR（677C→T）或MTRR（66A→G）的变异是否可能与除21三体之外的其他人类三体性疾病有关。我们分析了93例性染色体三体、44例18三体以及158例2、7、10、13、14、15、16、18或22号常染色体三体病例中母亲的MTHFR和MTRR多态性，并将基因型分布与对照人群进行了比较。我们观察到18三体胎儿的母亲中MTHFR多态性显著增加，但未能发现任何其他显著关联。总体而言，我们的观察结果表明，至少对于性染色体和一组常染色体三体综合征而言，叶酸代谢途径中的多态性并非人类减数分裂不分离的重要因素。
