To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China. Methods One hundred and ninety-two...To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China. Methods One hundred and ninety-two CHD patients and their parents were included in this study as case group in Liaoning Province by birth defect registration cards, and 124 healthy subjects (age and gender matched) and their parents were simultaneously selected from the same geographic area as control. Their gene polymorphism of MTHFD G1958A locus was examined with PCR-RFLP, and serum folic acid and homocysteine (Hcy) levels were tested with radio-immunoassay and fluorescence polarization immunoassay (FPIA). Results There existed gene polymorphism at MTHFD G1958A locus in healthy subjects living in North China. The percentages of GG, GA, and AA genotype were 57.98%, 35.57%, and 6.45% respectively, and the A allele frequency was 24.23%, which was significantly different from Western population. No difference was observed when comparing genotype distribution and allele frequency between the case and control groups, so was the result from the comparison between genders. The A allele frequency of arterial septal defect patients’ mothers (10.87%) was significantly lower than that of controls (28.15%) (P=0.014), with OR=0.31 (95% CI: 0.09-0.84), and no difference in the other subgroups. The percentage of at least one parent carrying A allele in arterial septal defect subgroup (43.48%) was significantly lower than that in controls (69.64%) (P=0.017), with OR=0.34 (95% CI: 0.12-0.92). The analysis of genetic transmission indicated that there was no transmission disequillibrium in CHD nuclear families. Their serum folic acid level was significantly higher than that of controls (P=0.000), and Hcy level of the former was higher than that of the latter with no statistical significance (P>0.05). Serum Hcy and folic acid levels of mothers with gene mutation were lower than those of mothers with no mutation. Conclusion No significant difference of genotype distribution and allele frequency existed between CHD patients and healthy population. MTHFD G1958A mutation in parents (particularly in mother) can decrease the risk of arterial septal defect in offspring. The possible mechanism of protection might be mutation, which can increase MTHFD enzyme activity, folic acid metabolism and homocysteine remethylation, and decrease Hcy level.展开更多
目的探讨在常规治疗基础上补充叶酸及B族维生素是否能改善冠心病（CHD）患者的血管内皮功能。方法经冠脉造影检查至少一支冠状动脉狭窄t〉50％的连续CHD患者87例，在包括阿司匹林及他汀类调脂药等的常规治疗基础上随机分为两组。试药组...目的探讨在常规治疗基础上补充叶酸及B族维生素是否能改善冠心病（CHD）患者的血管内皮功能。方法经冠脉造影检查至少一支冠状动脉狭窄t〉50％的连续CHD患者87例，在包括阿司匹林及他汀类调脂药等的常规治疗基础上随机分为两组。试药组（45例）：在常规治疗的基础上加服叶酸15mg／d；维生素K30mg／d；维生素B12：75μg／d；对照组（42例）：常规治疗。治疗半年，于治疗前后采用HP SONOS 5500型彩色超声显像仪和3．0～117．0MH：的线阵探头，分别测量患者休息时、反应性充血后肱动脉内径。比较治疗前后内皮依赖性血管舒张功能（flow-mediated dilation，FMD）的变化。结果治疗前，试药组与对照组间肱动脉基础内径[（4．2±0．5）mm vs（4．6±0．4）mm]及反应充血引起的肱动脉内径变化差异无统计学意义[（3．9±0．9）％ vs （4．1±0．5）％]。半年后两组患者反应充血引起的肱动脉内径变化均较自身治疗前明显改善[试药组（3．9±0．9）％ vs （15．5±5．4）％，P〈0．01；对照组[（4．1±5）％ vs （14．0±6．3）％，P〈0．01]，但两组反应充血引起的肱动脉内径变化差异无统计学意义[（15．5±5．4）％ vs （14．0±6．3）％]。结论含阿司匹林及他汀类调脂药的CHD常规治疗能明显改善CHD患者的血管内皮功能，在常规治疗基础上补充叶酸及B族维生素对改善CHD患者血管内皮功能的作用不优于CHD常规治疗。展开更多
基金This work was supported by the Major State Basic Research Development Program of People’s Republic of China (G1999055904)and the Danone’s Diet and Nutrition Research and Education Grant (DIC2002-08).
文摘To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China. Methods One hundred and ninety-two CHD patients and their parents were included in this study as case group in Liaoning Province by birth defect registration cards, and 124 healthy subjects (age and gender matched) and their parents were simultaneously selected from the same geographic area as control. Their gene polymorphism of MTHFD G1958A locus was examined with PCR-RFLP, and serum folic acid and homocysteine (Hcy) levels were tested with radio-immunoassay and fluorescence polarization immunoassay (FPIA). Results There existed gene polymorphism at MTHFD G1958A locus in healthy subjects living in North China. The percentages of GG, GA, and AA genotype were 57.98%, 35.57%, and 6.45% respectively, and the A allele frequency was 24.23%, which was significantly different from Western population. No difference was observed when comparing genotype distribution and allele frequency between the case and control groups, so was the result from the comparison between genders. The A allele frequency of arterial septal defect patients’ mothers (10.87%) was significantly lower than that of controls (28.15%) (P=0.014), with OR=0.31 (95% CI: 0.09-0.84), and no difference in the other subgroups. The percentage of at least one parent carrying A allele in arterial septal defect subgroup (43.48%) was significantly lower than that in controls (69.64%) (P=0.017), with OR=0.34 (95% CI: 0.12-0.92). The analysis of genetic transmission indicated that there was no transmission disequillibrium in CHD nuclear families. Their serum folic acid level was significantly higher than that of controls (P=0.000), and Hcy level of the former was higher than that of the latter with no statistical significance (P>0.05). Serum Hcy and folic acid levels of mothers with gene mutation were lower than those of mothers with no mutation. Conclusion No significant difference of genotype distribution and allele frequency existed between CHD patients and healthy population. MTHFD G1958A mutation in parents (particularly in mother) can decrease the risk of arterial septal defect in offspring. The possible mechanism of protection might be mutation, which can increase MTHFD enzyme activity, folic acid metabolism and homocysteine remethylation, and decrease Hcy level.
文摘目的探讨在常规治疗基础上补充叶酸及B族维生素是否能改善冠心病（CHD）患者的血管内皮功能。方法经冠脉造影检查至少一支冠状动脉狭窄t〉50％的连续CHD患者87例，在包括阿司匹林及他汀类调脂药等的常规治疗基础上随机分为两组。试药组（45例）：在常规治疗的基础上加服叶酸15mg／d；维生素K30mg／d；维生素B12：75μg／d；对照组（42例）：常规治疗。治疗半年，于治疗前后采用HP SONOS 5500型彩色超声显像仪和3．0～117．0MH：的线阵探头，分别测量患者休息时、反应性充血后肱动脉内径。比较治疗前后内皮依赖性血管舒张功能（flow-mediated dilation，FMD）的变化。结果治疗前，试药组与对照组间肱动脉基础内径[（4．2±0．5）mm vs（4．6±0．4）mm]及反应充血引起的肱动脉内径变化差异无统计学意义[（3．9±0．9）％ vs （4．1±0．5）％]。半年后两组患者反应充血引起的肱动脉内径变化均较自身治疗前明显改善[试药组（3．9±0．9）％ vs （15．5±5．4）％，P〈0．01；对照组[（4．1±5）％ vs （14．0±6．3）％，P〈0．01]，但两组反应充血引起的肱动脉内径变化差异无统计学意义[（15．5±5．4）％ vs （14．0±6．3）％]。结论含阿司匹林及他汀类调脂药的CHD常规治疗能明显改善CHD患者的血管内皮功能，在常规治疗基础上补充叶酸及B族维生素对改善CHD患者血管内皮功能的作用不优于CHD常规治疗。
