Department of Gynecology, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, No.253, Gongye Middle Avenue, Haizhu District, 510280, Guangzhou, Guangdong, China.
Clinical Research Center, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China.
Reprod Biol Endocrinol. 2021 Jan 7;19(1):5. doi: 10.1186/s12958-020-00688-8.
The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level.
A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level.
Following adjustments and multiple rounds of testing, MTHFR A1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRR A66G was nominally associated with PCOS. Mutations in MTHFR A1298C and MTRR A66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFR A1298C on PCOS was mediated by homocysteine.
MTHFR A1298C and MTRR A66G were associated with PCOS, and MTHFR A1298C might affect the risk of PCOS by influencing the homocysteine level.
同型半胱氨酸与多囊卵巢综合征（PCOS）之间的病因关系尚不清楚。在人类中，同型半胱氨酸水平主要受两种酶的影响：亚甲基四氢叶酸还原酶（MTHFR）和蛋氨酸合成酶还原酶（MTRR）。这两种酶的活性主要受三个错义突变的影响，即 C677T（MTHFR）、A1298C（MTHFR）和 A66G（MTRR）。本研究旨在探讨这三种错义突变与 PCOS 之间的关联，并研究这三种错义突变是否通过影响同型半胱氨酸水平对 PCOS 产生影响。
设计了一项病例对照研究，纳入了 150 名 PCOS 患者和 300 名对照。采用 logistic 回归分析评估三种错义突变与 PCOS 的关联。采用线性回归分析评估三种错义突变与同型半胱氨酸水平的关联。采用中介分析探讨三种错义突变是否通过影响同型半胱氨酸水平对 PCOS 产生影响。
经过调整和多轮测试，发现 MTHFR A1298C 与 PCOS 呈剂量依赖性显著相关（与 AA 相比，AC 的 OR=2.142，CC 的 OR=3.755；P<0.001）。MTRR A66G 与 PCOS 有一定的关联。MTHFR A1298C 和 MTRR A66G 的突变与同型半胱氨酸水平显著相关。中介分析表明，MTHFR A1298C 对 PCOS 的影响是通过同型半胱氨酸介导的。
MTHFR A1298C 和 MTRR A66G 与 PCOS 相关，MTHFR A1298C 可能通过影响同型半胱氨酸水平影响 PCOS 的发病风险。
