Sayadi Mohamed Amine, Achour Ons, Ezzaher Asma, Hellara Ilham, Omezzine Asma, Douki Wahiba, Bousslama Ali, Gaha Lotfi, Najjar Mohamed Fadhel
Laboratory of Biochemistry-Toxicology, Monastir University Hospital, Monastir, Tunisia ; Research Laboratory "Vulnerability to Psychotic disorders LR 05 ES 10", Department of Psychiatry, Monastir University Hospital, Monastir, Tunisia.
LR 12 SP 11, Biochemistry Department, Sahloul Sousse University Hospital, Sousse, Tunisia.
Ann Gen Psychiatry. 2016 Jul 30;15:18. doi: 10.1186/s12991-016-0103-5. eCollection 2016.
Major depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis. The aim of this research is to study the association between the C677T polymorphism of MTHFR gene and depression in Tunisian population, to explore their relationship with clinical and therapeutic characteristics of this disease. And it may lead to discover a novel marker to identify a patient with a higher risk of development of depressive disorder to be. This marker can be used for better therapeutic management and prevent disease installation.
Our study included 208 depressive patients, 187 controls aged between 44.1 ± 13.5 and 38.9 ± 13.2 years, respectively. MTHFR gene polymorphisms were determined by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism).
No significant difference was detected in the distribution of the genotype frequencies of MTHFR C677T polymorphisms (χ (2) = 5.443, df = 2, p = 0.066) between patients and controls. But when we study the risk of these genotypes, CT genotype is significantly more frequent in controls compared to patients, it may be a protection from depression (OR = 0.655, CI 95 % = 0.432-0.995, p = 0.047, OR* = 0.638, CI 95 %* = 0.415-0.983, p* = 0.04, before and after adjustment). Women, TT Genotype can increase four times the risk to be depressive. Addictive behavior seems to be associated with CT genotype and there was no significant association between clinical and therapeutic characteristics and this polymorphism.
This paper is the first study to prove that CT genotype of MTHFR C677T polymorphism may protect from depression and TT genotype seems to be associated with women's depression. Further studies are required with other polymorphisms and biochemical factors that must be investigated to clarify the implication of MTHFR C677T polymorphism in the pathophysiology of depression.
重度抑郁症（MDD）是一种常见的精神疾病，具有较高的死亡率。非自然原因导致的死亡，主要是自杀或准自杀，对于功能障碍，尤其是抑郁症和精神分裂症，具有特别高的风险。这种疾病的一个前瞻性风险因素是高同型半胱氨酸血症和叶酸缺乏。亚甲基四氢叶酸还原酶（MTHFR）基因编码一种参与叶酸代谢和神经递质合成的5-亚甲基四氢叶酸还原酶。本研究的目的是探讨突尼斯人群中MTHFR基因C677T多态性与抑郁症之间的关联，以探索它们与该疾病临床和治疗特征的关系。这可能会发现一种新的标志物，用于识别患抑郁症风险较高的患者。该标志物可用于更好的治疗管理和预防疾病的发生。
我们的研究纳入了208名抑郁症患者和187名对照，年龄分别在44.1±13.5岁和38.9±13.2岁之间。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）测定MTHFR基因多态性。
患者和对照之间MTHFR C677T多态性的基因型频率分布没有显著差异（χ² = 5.443，自由度 = 2，p = 0.066）。但当我们研究这些基因型的风险时，与患者相比，CT基因型在对照中显著更常见，它可能对抑郁症具有保护作用（优势比（OR）= 0.655，95%置信区间（CI）= 0.432 - 0.995，p = 0.047，调整前后的OR* = 0.638，95%CI* = 0.415 - 0.983，p* = 0.04）。对于女性，TT基因型可使患抑郁症的风险增加四倍。成瘾行为似乎与CT基因型有关，并且临床和治疗特征与这种多态性之间没有显著关联。
本文是首次证明MTHFR C677T多态性的CT基因型可能对抑郁症具有保护作用，而TT基因型似乎与女性抑郁症有关。需要进一步研究其他多态性和生化因素，以阐明MTHFR C677T多态性在抑郁症病理生理学中的作用。
