Ozkul Y, Evereklioglu C, Borlu M, Taheri S, Calis M, Dündar M, Ilhan O
Sivas Cad Cebeci Apt A-Blok, 175/15, TR-38020, Kayseri, Turkey.
Br J Ophthalmol. 2005 Dec;89(12):1634-7. doi: 10.1136/bjo.2005.076836.
Increased serum levels of homocysteine (Hcy) have been reported in patients with Behçet's disease (BD) with an established risk factor for vascular involvement. Recently, the authors demonstrated that elevated Hcy levels are associated with ocular involvement in such patients. On the other hand, elevated levels of Hcy can result from genetic errors. Indeed, a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) gene influences Hcy metabolism and, therefore, MTHFR C677T polymorphism provokes hyperhomocysteinaemia.
To investigate the possible genetic factor for the elevation of plasma Hcy level in patients with BD by examining gene interaction with the MTHFR C677T polymorphism, a crucial factor of the Hcy metabolism. In addition, the authors aimed to evaluate if there is an association between the C677T polymorphism and the presence of ocular involvement in such patients.
A total of 59 patients with BD (25 men, 34 women) with a mean age of 34.9 years and 42 age and sex matched healthy control subjects (19 men, 23 women; mean age 32.2) were included in this investigation. MTHFR gene polymorphism was investigated by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of a genomic DNA fragment at nucleotide 677 in all subjects in both groups. The genetic equilibrium is assumed for the gene frequencies of the MTHFR polymorphism in both samples.
The genotype of the MTHFR gene differed between the Behçet's patients and control subjects (TT: 11.9 v 2.4%; CT: 55.9 v 61.9%; CC: 32.2 v 35.7 %). TT homozygous genotype was more frequently in BD patients than the controls, though the difference was not significant (p = 0.063). In BD patients with ocular involvement, however, the frequencies of MTHFR TT homogenetic type (27.8%) were significantly and statistically higher than those in BD patients without ocular involvement (4.9%, p = 0.022, odds ratio = 7.5), or the controls (2.4%, p = 0.003, odds ratio = 20.0). TT homozygous genotype was associated with an increased risk for ocular involvement.
Elevated serum levels of Hcy seem to be a result of C677T polymorphism of the MTHFR gene, with increased TT individuals over CC and CT genotype BD patients. Although no association was shown between the MTHFR reductase C677T polymorphism and the increased risk of oral aphtahe or genital ulcers, a mutation in this gene was associated with an increased risk of ocular involvement, suggesting genetic instability with a potential initiation of Hcy lowering therapy in this patient group.
白塞病（BD）患者血清同型半胱氨酸（Hcy）水平升高，这是血管受累的既定危险因素。最近，作者证明此类患者中Hcy水平升高与眼部受累有关。另一方面，Hcy水平升高可能由基因缺陷导致。事实上，5,10 - 亚甲基四氢叶酸还原酶（MTHFR C677T）基因的突变会影响Hcy代谢，因此，MTHFR C677T基因多态性会引发高同型半胱氨酸血症。
通过研究与Hcy代谢关键因素MTHFR C677T基因多态性的基因相互作用，调查BD患者血浆Hcy水平升高可能的遗传因素。此外，作者旨在评估C677T基因多态性与此类患者眼部受累情况之间是否存在关联。
本研究纳入了59例BD患者（25例男性，34例女性），平均年龄34.9岁，以及42例年龄和性别匹配的健康对照者（19例男性，23例女性；平均年龄32.2岁）。通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）对两组所有受试者基因组DNA片段中核苷酸677处的MTHFR基因多态性进行研究。假定两组样本中MTHFR多态性的基因频率处于遗传平衡状态。
BD患者和对照者的MTHFR基因基因型不同（TT：11.9%对2.4%；CT：55.9%对61.9%；CC：32.2%对35.7%）。BD患者中TT纯合基因型的频率高于对照组，尽管差异不显著（p = 0.063）。然而，在有眼部受累的BD患者中，MTHFR TT纯合型的频率（27.8%）显著高于无眼部受累的BD患者（4.9%，p = 0.022，优势比 = 7.5），或对照组（2.4%，p = 0.003，优势比 = 20.0）。TT纯合基因型与眼部受累风险增加相关。
血清Hcy水平升高似乎是MTHFR基因C677T多态性的结果，TT个体在BD患者中的比例高于CC和CT基因型患者。虽然未显示MTHFR还原酶C677T多态性与口腔溃疡或生殖器溃疡风险增加之间存在关联，但该基因突变与眼部受累风险增加相关，这表明该患者群体存在遗传不稳定性，可能需要启动降低Hcy的治疗。
