中老年高同型半胱氨酸血症基因多态性与叶酸治疗效果的关联性研究

Association between gene polymorphisms related to hyperhomocysteinemia and the folic acid treatment effect in middle-aged and elderly

目的 探讨中老年高同型半胱氨酸血症(HHcy)相关基因多态性与叶酸补充效果的关联性。方法 2020年1~12月于宜宾市第一人民医院确诊的中老年HHcy患者334例,采用问卷收集一般资料,抽取清晨空腹血测定同型半胱氨酸(Hcy)浓度,采用PCR荧光探针法和实时定量荧光PCR(RT-PCR)法检测外周血基因组DNA中MTHFR基因C677T(rs1801133)、A1298C(rs1801131)和MTRR基因A66G (rs1801394)多态性位点,比较不同情况HHcy患者MTHFR基因C677T、A1298C和MTRR基因A66G基因型构成比和等位基因频率。结果 MTHFR基因C677T位点TT型、A1298C位点CC型和MTRR基因A66G位点GG型占比分别为46.7%、16.2和13.5%,rs1801133 T等位基因、rs1801131 C等位基因和rs1801394 G等位基因占比分别为63.3%、29.0%和29.0%。不同居住地、民族和吸烟饮酒史的rs1801131基因型分布比较,差异有统计学意义(P<0.05),不同居住地、BMI及吸烟饮酒史的rs1801394基因型分布比较,差异有统计学意义(P<0.05)。叶酸治疗无效组MTHFR基因T677T和C1298C频率及rs1801133 T等位基因和rs1801131 C等位基因频率高于有效组(P<0.05)。结论 MTHFR的T677T和C1298C患者叶酸治疗效果差。

Objective To explore the association between gene polymorphisms related to hyperhomocysteinemia(HHcy) and effects of folic acid supplementation in middle-aged and elderly people.Methods From January to December 2020, 334 patients with HHcy were selected from our hospital. General data were collected by questionnaires. Morning fasting blood was drawn to measure homocysteine(Hcy) concentration. PCR fluorescent probe method and real-time quantitative fluorescent PCR(RT-PCR) method were used to detect the polymorphisms of methylenetetrahydrofolate reductase(MTHFR) gene at C677 T(rs1801133) and A1298 C(rs1801131) as well as methionine synthesis reductase(MTRR) gene at A66 G(rs1801394) in peripheral blood genomic DNA. The genotype composition ratio and allele frequency of MTHFR gene at C677 T and A1298 C and MTRR gene at A66 G in HHcy patients under different conditions were compared.Results The proportions of TT genotype at C677 T locus, CC genotype at A1298 C locus and GG genotype at A66 G locus were 46.7%, 16.2% and 13.5%, respectively. The proportions of rs1801133 T allele, rs1801131 C allele and rs1801394 G allele were 63.3%, 29.0% and 29.0%, respectively. The genetype of rs1801131 were different among HHcy patients with different habitation, nationality and history of smoking or drinking. The genetype of rs1801394 were also different among different habitation, body mass index(BMI) and history of smoking or drinking. All differences were statistically significant(P<0.05). After 3 months folic acid supplementation, the distribution frequencies of MTHFR gene T677 T and C1298 C and the frequencies of 677 T allele and 1298 C allele in the ineffective group were higher than those in the effective group(P<0.05).Conclusion The therapeutic effect of folic acid is poor in the patients with T677 T and C1298 C genotype of MTHFR.