血管性痴呆患者的MTHFR基因多态性与血清Hcy水平变化及其交互作用

Changes and interactions between MTHFR gene polymorphisms and serum Hcy levels in patients with vascular dementia

目的探讨甲基四氢叶酸还原酶(Methylene tetrahydrofolate reductase,MTHFR)-C677T基因多态性与同型半胱氨酸(Homocysteine,Hcy)的交互作用对血管性痴呆的影响。方法选取2021年5月-2023年5月于本院收治的血管性痴呆患者104例设为观察组,选取同期于本院体检的健康志愿者112例设为对照组;比较2组的一般资料;检测2组患者的MTHFR-C677T多态性位点基因型及等位基因频率分布;分析MTHFR-C677T单核苷酸多态性(Single nucleotide polymorphism,SNP)与血管性痴呆易感性的关系;比较MTHFR-C677T携带C基因型不同等位基因型血管性痴呆患者的临床特征;采用样条函数与Logistic回归结合的限制性立方样条法分析血管性痴呆与血清Hcy水平关联强度的剂量反应;通过多因素Logistic回归分析血管性痴呆发病的危险因素;采用相加和相乘模型对血管性痴呆的影响因素进行交互作用分析。结果2组在维生素B_(12)(Vitamin B_(12),VitB_(12))、基质金属蛋白酶9(Matrix metalloproteinase-9,MMP-9)、Nod样受体蛋白3(Nodlike receptor protein 3,NLRP3)、Hcy、超敏C-反应蛋白(Hypersensitive-C-reactive protein,hs-CRP)、D-二聚体(D-dimer,D-D)、叶酸(Frolic acid,FA)方面均有明显差异(P<0.05);基因分型后得纯合TT片段为175 bp和23 bp,杂合CT型片段为198 bp、175 bp和23 bp,纯合子CC型片段为198 bp;2组的CC、CT、TT基因频率均有明显差异(P<0.05);对于血管性痴呆的病情加重风险,C等位基因携带者比未携带者增加36.92%[OR(95%CI)=1.377(1.12~2.01)],而CC型基因携带者是未携带者的1.63倍;限制性立方样条模型表明,Hcy值的连续性变化与发生血管性痴呆的关联强度呈现非线性剂量反应关系(P<0.01);MMP-9<27.12 pg/mL,Hcy<14.34μmol/L,MTHFR携带C基因型是导致血管性痴呆发病的独立危险因素(P<0.05);相加和相乘模型显示MMP-9<27.12 pg/mL,Hcy<14.34μmol/L,MTHFR携带C基因型两两之间皆存在交互作用。结论血清Hcy水平升高与MTHFR基因C677T突变均是血管性痴呆的危险因素且两者之间存在交互作用。

Objective To explore the impact of the interaction between the MTHFR gene polymorphism and homocysteine(Hcy)on vascular dementia.Methods A total of 104 patients with vascular dementia admitted to our hospital between May 2021 and May 2023 were selected as the observation group,and 112 healthy volunteers who underwent physical examination at our hospital during the same period were selected as the control group.The general data of the two groups were compared,the genotypes and allele frequencies of the MTHFR-C677T polymorphisms in the two groups were detected,the relationship between the MTHFR-C677T single nucleotide polymorphism(SNP)and vascular dementia was analyzed,and the clinical characteristics of vascular dementia patients with different allele C genotypes of MTHFR-C677T were compared.The dose response to vascular dementia and the serum Hcy concentration were analyzed via the restricted cubic spline method combined with spline function and logistic regression.The risk factors for vascular dementia were analyzed via multivariate logistic regression,and the interaction factors for vascular dementia were analyzed via additive and multiplicative model.Results There were significant differences in vitamin B12(VB12),matrix metalloproteinase-9(MMP-9),nod-like receptor protein 3(NLRP3),Hcy,hypersensitive C-reactive protein(hs-CRP),D-dimer(D-D)and folic acid(FA)between the two groups.The homozygous TT fragments were 175 bp and 23 bp,the heterozygous CT fragments were 198 bp,175 bp and 23 bp,and the homozygous CC fragments were 198 bp.There were significant differences in CC,CT and TT gene frequencies between the two groups.For the risk of severe pneumonia aggravation in the elderly population,the risk was 36.92%greater in C allele carriers than in noncarriers[OR(95%CI)=1.377(1.12~2.01)],while the risk was 1.63 times greater in CC genotype carriers than in noncarriers.The restricted cubic spline model showed that there was a nonlinear dose-response relationship between continuous changes in the HCy value and the occurrence of vascular dementia,and an MMP-9 concentration<27.12 pg/mL,a Hcy concentration<14.34μmol/L and the MTHFR carrying the C genotype were found to be independent risk factors for vascular dementia.Additive and multiplicative models revealed interactions between MMP-9 concentrations<27.12 pg/mL and Hcy concentrations<14.34μmol/L and between MTHFR and the C genotype.Conclusion Both elevated serum Hcy levels and the C677T mutation in the MTHFR gene are risk factors for vascular dementia,and there is an interaction between them.