Abnormal folate metabolism is a risk factor for DNA hypomethylation and chromosomal nondisjunction. MTHFR is a candidate gene for folliculogenesis and ovarian development. In the present study, we aimed to investigate the distribution of the MTHFR C677T polymorphism in individuals with primary amenorrhea and it’s association with the cytogenetic and clinical profile. The MTHFR polymorphism (C677T) was checked in 45 females with PA and 45 control females (age-matched) with regular menstrual cycles using polymerase chain reaction-restriction fragment length polymorphism. We observed the CC genotype in 84.4% (n = 38) of the control group females and 48.9% (n = 22) of the case group females, CT genotype in 13.3% (n = 6) in the control group females and 24.4% (n = 11) in the case group females (p = 0.039; χ2 value 4.253; odd ratio 0.316, 95%CI 0.103–0.973) and TT genotype in 2.2% (n = 1) in the control group females and 26.7% (n = 12) in the case group females (p = 0.000266; χ2 value 13.294; odd ratio 0.048, 95%CI 0.006–0.397). Out of 45 case group females, 26 females showed 46,XX karyotype, 4 females showed male karyotype, 3 females showed pure Turner karyotype, 2 females were mosaic Turner and the rest of the females showed structural abnormalities like deletion, isochromosome and normal variants. The serum values revealed significantly lower levels (p = 0.032) of progesterone in the individuals with the TT genotype as compared to the CC genotype and the radiology profile showed a significant role of the MTHFR gene in ovarian development (p = 0.024). We suggest that the MTHFR polymorphism (C677T) might be responsible for the chromosomal nondisjunction in monosomy X females. It also influences the progesterone level and ovarian development, thus affecting folliculogenesis and the ovarian reserve responsible for primary amenorrhea.

中文翻译：

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MTHFR (C677T) 多态性及其与原发性闭经个体细胞遗传学和临床特征的关联

叶酸代谢异常是 DNA 低甲基化和染色体不分离的危险因素。MTHFR 是卵泡发生和卵巢发育的候选基因。在本研究中，我们旨在探讨 MTHFR C677T 多态性在原发性闭经个体中的分布及其与细胞遗传学和临床特征的关系。使用聚合酶链反应-限制性片段长度多态性检查 45 名患有 PA 的女性和 45 名月经周期规律的对照女性（年龄匹配）的 MTHFR 多态性 (C677T)。我们观察到对照组女性中 84.4% (n = 38) 和病例组女性中 48.9% (n = 22) 存在 CC 基因型，对照组女性中 13.3% (n = 6) 和 24.4% 中观察到 CT 基因型(n = 11) 在病例组女性中 (p = 0.039; χ2 值 4.253; 奇数比 0.316, 95%CI 0.103–0.973) 和 TT 基因型在对照组女性中为 2.2% (n = 1) 和 26.7% ( n = 12) 病例组女性 (p = 0.000266; χ2 值 13.294; 奇数比 0.048, 95%CI 0.006–0.397)。45例女性病例中，26例为46，XX核型，4例为男性核型，3例为纯Turner核型，2例为嵌合型Turner，其余为缺失、等染色体、正常变异等结构异常。血清值显示，与 CC 基因型相比，TT 基因型个体的孕酮水平显着降低 (p = 0.032)，放射学特征显示 MTHFR 基因在卵巢发育中发挥重要作用 (p = 0.024)。我们认为 MTHFR 多态性 (C677T) 可能是 X 单体雌性染色体不分离的原因。它还影响黄体酮水平和卵巢发育，从而影响卵泡发生和导致原发性闭经的卵巢储备。