Zittan E, Preis M, Asmir I, Cassel A, Lindenfeld N, Alroy S, Halon D A, Lewis B S, Shiran A, Schliamser J E, Flugelman M Y
Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, 7 Michal Street, Haifa, Israel 34632.
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H860-5. doi: 10.1152/ajpheart.01189.2006. Epub 2007 Apr 20.
The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 +/- 18.8 vs. 9.4 +/- 3.2 mumol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.1-8.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.
本研究旨在检测360名无症状个体中，亚甲基四氢叶酸还原酶（MTHFR）C677T突变纯合性与维生素B12缺乏之间的关联，并研究C677T纯合子的前臂内皮功能。对研究参与者检测了MTHFR C677T突变以及维生素B12、叶酸和同型半胱氨酸水平。C677T突变纯合性的频率为67/360（18.6%）。与杂合子受试者或无该突变的受试者相比，纯合子的同型半胱氨酸水平升高（20.6±18.8 vs. 9.4±3.2 μmol/l；P<0.0001）。纯合子中维生素B12缺乏（<150 pmol/l）的受试者数量显著高于杂合子受试者或无突变的受试者[20/67（29.8%） vs. 27/293（9.2%）；P<0.0001]。纯合子受试者发生B12缺乏的可能性高4.2倍（95%置信区间=2.1-8.3）。对33名纯合子和12名对照受试者进行了前臂内皮功能评估。在纯合子受试者中观察到内皮功能异常，且在伴有维生素B12缺乏的纯合子受试者中更严重。维生素B12和叶酸治疗后内皮功能恢复正常。我们发现，C677T突变纯合性与B12缺乏密切相关。C677T突变纯合性与B12缺乏共存与内皮功能障碍有关，且可用维生素B12和叶酸治疗纠正。
