外阴上皮内非瘤样病变患者MTHFRC677T基因多态性研究

MTHFRC677T gene polymorphism in patients with nonneoplastic epithelial disorders of vulva

目的:探讨外阴上皮内非瘤样病变(nonneoplastic epithelial disorders of vulva,NNEDV)的发生与N5,10-亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)C677T基因多态性的关系及可能机制。方法:回顾性分析2016年8月至2018年6月于我院就诊最终经活检确诊为NNEDV的患者共60例(研究组)及同时期健康体检女性46例(对照组),比较2组中MTHFRC677T基因多态性差异及不同病理类型的NNEDV患者血清叶酸、血同型半胱氨酸及MTHFRC677T基因多态性差异。其中研究组包括外阴慢性单纯性苔藓(lichen simplex chronicus,LSC)患者21例,外阴硬化性苔藓(lichen sclerosus,LS)患者39例。结果:研究组MTHFR 677TT基因型所占比率(13.3%)及T等位基因比率(38.3%)均较对照组(4.3%,21.7%)明显升高,差异均有统计学意义(χ^2=6.851,P=0.033;χ^2=6.688,P=0.010);LSC患者MTHFR677TT基因型比率(23.8%)及T等位基因比率(45.2%)较对照组明显升高,差异均有统计学意义(χ^2=7.572,P=0.023;χ^2=7.717,P=0.005);LS患者MTHFR677TT基因型比率(7.7%)及T等位基因比率(34.6%)介于对照组与LSC患者间,两两比较差异均无统计学意义(P>0.05)。与CC基因型相比,CT、TT基因型可能增加NNEDV发生的风险,其OR值分别为2.386(95%CI=1.046~5.443)和5.091(95%CI=0.981~26.430)。在MTHFR677CC型、CT型及TT型患者中,随着突变基因T的增加,其血清叶酸逐渐下降,差异有统计学意义(F=4.386,P=0.018),血同型半胱氨酸逐渐升高,差异有统计学意义(F=4.978,P=0.012),不同病理类型的NNEDV患者血清叶酸及血同型半胱氨酸水平均无明显统计学差异(P>0.05)。结论:MTHFRC677T基因突变导致的血清叶酸及血同型半胱氨酸代谢障碍可能与LSC的发生有关。

Objective:To examine the relationship between N5,10-methylenetetrahydrofolate reductase(MTHFR)C677 T gene polymorphism and nonneoplastic epithelial disorders of vulva(NNEDV),and its possible mechanism of action. Methods:The clinical data of 60 patients NNEDV confirmed by biopsy(study group)and 46 healthy women(control group)in our hospital between August 2016 to June 2018 were reviewed. MTHFRC677 T gene polymorphism was compared between the two groups. In addition,MTHFRC677 T gene polymorphism and serum folic acid and serum homocysteine levels were also compared between patients with different histopathologic types of NNEDV. The study group included 21 cases of vulvar lichen simplex chronicus(LSC)and 39 cases of vulvar lichen sclerosus(LS). Results:The frequencies of the MTHFR 677 TT genotype and T allele were significantly increased in the study group(13.3% and 38.3%,respectively)than in the control group(4.3% and 21.7%,respectively)(χ^2=6.851,P=0.033;χ^2=6.688,P=0.010,respectively). Compared with the control group,LSC patients had significantly increased frequencies of MTHFR 677 TT genotype(23.8%)and T allele(45.2%)(χ^2=7.572,P=0.023;χ^2=7.717,P=0.005,respectively). In contrast,there no significant differences in the frequencies of the MTHFR 677 TT genotype(7.7%)and T allele(34.6%)between LS patients and controls(both P>0.05). Compared with the CC genotype,the CT(OR=2.386,95% CI=1.046 to 5.443) and TT(OR=5.091,95% CI=0.981 to 26.430)genotypes might increase the risk of NNEDV. In patients with the MTHFR677 CC,CT,and TT genotypes,serum folic acid level significantly decreased(F =4.386,P =0.018) and serum homocysteine level significantly increased(F=4.978,P=0.012) as the number of T mutations increased. However,there were no significant differences in serum folic acid and homocysteine levels between LSC and LS patients(both P >0.05). Conclusion:Serum folic acid and homocysteine dysmetabolism induced by MTHFRC677 T gene mutation may be associated with the development of LSC.