An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women.
An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women.
复制标题
二氢叶酸还原酶 (DHFR) 基因的插入/缺失多态性与女性血清和红细胞叶酸浓度相关。
DOI：
10.1007/s00439-008-0475-y
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发表时间：
2008
期刊：
影响因子：
5.3
通讯作者：
Whitehead,AlexanderS
中科院分区：
文献类型：
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作者：
Stanisławska-Sachadyn,Anna;Brown,KarenS;Mitchell,LauraE;Woodside,JayneV;Young,IanS;Scott,JohnM;Murray,Liam;Boreham,ColinA;McNulty,Helene;Strain,JJ;Whitehead,AlexanderS
低血清叶酸和高同型半胱氨酸与神经管缺陷(NTDS)、心血管疾病和其他病理疾病的风险增加相关。因此，明确可能影响叶酸/同型半胱氨酸代谢的遗传和非遗传因素将有助于我们对这些疾病的病因机制的理解，并有助于风险评估。二氢叶酸还原酶催化叶酸还原为二氢叶酸，然后还原为四氢叶酸。二氢叶酸还原酶(DHFR)c.86+6078插入/缺失(INS/Del)多态对叶酸和同型半胱氨酸浓度的影响使用了来自北爱尔兰的健康年轻人的数据，这些数据是作为青年心脏项目访问三的一部分收集的。在男性中，DHFRc.86+60_78基因多态与血清或红细胞叶酸浓度或同型半胱氨酸浓度没有显著相关性。在女性中，DHFRc.86+60_78基因多态可以解释2%的红细胞叶酸水平和5%的血清叶酸水平的变化，但对同型半胱氨酸似乎没有独立的影响。与携带DHFRc.86+60_78 Ins/Ins和Ins/del基因的女性相比，del/del纯合子的血清和红细胞叶酸浓度升高，因此可能降低了子代受NTDS影响的风险，以及因叶酸过低而导致的其他不良生殖和健康后果。
A low serum folate and high homocysteine phenotype is associated with an increased risk of neural tube defects (NTDs), cardiovascular diseases and other pathologies. Thus defining both genetic and non-genetic factors that may impact folate/homocysteine metabolism will enhance our understanding of the etiologic mechanisms underlying these conditions and facilitate risk assessment. Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate. The impact of the dihydrofolate reductase (DHFR) c.86 + 60_78 insertion/deletion (ins/del) polymorphism on folate and homocysteine concentrations was analyzed using data from healthy young adults from Northern Ireland, collected as part of visit three of the Young Hearts Project. Among men theDHFRc.86 + 60_78 polymorphism was not significantly associated with serum or red blood cell folate concentrations, or with homocysteine concentrations. Among women theDHFRc.86 + 60_78 polymorphism explained 2% of the variation in RBC folate levels and 5% of the variation in serum folate levels, but did not appear to have an independent effect on homocysteine. Relative to women with theDHFRc.86 + 60_78 ins/ins and ins/del genotypes, del/del homozygotes had increased serum and red blood cell folate concentrations and may therefore be at decreased risk of having offspring affected by NTDs and of other adverse reproductive and health outcomes attributable to low folate.