Department of Medical Genetics, Kayseri Training and Research Hospital, Kayseri, Turkey.
Department of Clinical Biochemistry, Ataturk Training and Research Hospital, Ankara, Turkey.
Rheumatol Int. 2018 Jan;38(1):97-104. doi: 10.1007/s00296-017-3914-z. Epub 2017 Dec 19.
Many studies have shown that oxidative stress levels increase in patients with Familial Mediterranean Fever (FMF). Thiols are a class of compounds that include a sulfhydryl group (-SH) and can react with free oxygen radicals to protect tissues. We aimed to investigate thiol-disulphide homeostatic status in FMF patients and examined the effect of different mutations in the MEFV gene on the thiol-disulphide balance. We investigated thiol-disulphide parameters in patients with FMF and healthy controls. To determine the differential effect of MEFV gene mutations on thiol-disulphide balance, subjects were divided into five groups based on homozygous or compound heterozygous exon 10 and nonexon 10 mutations. Tests of thiol-disulphide homeostasis were conducted using the automated spectrophotometric method. Patients with FMF had significantly lower native thiol [433.8 µmol/l (243.3-536.4) vs. 484.1 µmol/L (340.2-612.3), p < 0.001], total thiol levels [459.7 µmol/L (281.3-575.4) vs. 529.9 µmol/L (363-669.5), p < 0.001], and disulphide levels [14.0 µmol/l (2.7-33.3) vs. 24.4 µmol/l (7.2-36.6), p < 0.001] compared to the control group. Moreover, disulphide/native thiol (3.4 ± 1.7 vs. 4.7 ± 1.3, p < 0.001) and disulphide/total thiol (3.1 ± 1.4 vs. 4.3 ± 1.0 p < 0.001) were also detected lower in the FMF group compared to the control group. But the native thiol/total thiol ratios (93.6 ± 2.9 vs. 91.3 ± 2.1, p < 0.001) were higher in the FMF group. There was no significant difference between the native thiol, total thiol, and disulphide levels of individuals with nonexon 10 homozygous or compound heterozygous (Group 1), nonexon 10-exon 10 compound heterozygous (Group 2), exon 10 homozygous or compound heterozygous (Group 3), and heterozygous (Group 4) mutations. However, these parameters significantly differed from those of the healthy control group. Since no differences were found in our study between thiol and disulfide levels of Groups 1, 2 and 3, we believe that this rate cannot be shown as an indicator of oxidative damage in different mutations of FMFs. To the best of our knowledge, this study is the first study that demonstrates the effect of different FMF mutations on the thiol-disulphide balance.
许多研究表明，家族性地中海热（FMF）患者的氧化应激水平升高。硫醇是一类包含巯基（-SH）的化合物，可与自由基反应，从而保护组织。我们旨在研究 FMF 患者的硫醇-二硫键稳态，并研究 MEFV 基因的不同突变对硫醇-二硫键平衡的影响。我们研究了 FMF 患者和健康对照组的硫醇-二硫键参数。为了确定 MEFV 基因突变对硫醇-二硫键平衡的差异影响，根据纯合或复合杂合外显子 10 和非外显子 10 突变，将受试者分为五组。使用自动化分光光度法检测硫醇-二硫键稳态。FMF 患者的天然巯基[433.8 µmol/L（243.3-536.4）比 484.1 µmol/L（340.2-612.3），p < 0.001]、总巯基水平[459.7 µmol/L（281.3-575.4）比 529.9 µmol/L（363-669.5），p < 0.001]和二硫键水平[14.0 µmol/L（2.7-33.3）比 24.4 µmol/L（7.2-36.6），p < 0.001]均显著低于对照组。此外，与对照组相比，FMF 组的二硫键/天然巯基（3.4 ± 1.7 比 4.7 ± 1.3，p < 0.001）和二硫键/总巯基（3.1 ± 1.4 比 4.3 ± 1.0，p < 0.001）也较低。但是，FMF 组的天然巯基/总巯基比值（93.6 ± 2.9 比 91.3 ± 2.1，p < 0.001）较高。外显子 10 纯合或复合杂合（第 1 组）、外显子 10-非外显子 10 复合杂合（第 2 组）、非外显子 10 纯合或复合杂合（第 3 组）和杂合（第 4 组）突变个体的天然巯基、总巯基和二硫键水平无显著差异。然而，这些参数与健康对照组有显著差异。由于我们的研究在第 1、2 和 3 组中未发现巯基和二硫化物水平之间的差异，我们认为该比率不能作为 FMF 不同突变的氧化损伤的指标。据我们所知，这项研究首次表明不同的 FMF 突变对硫醇-二硫键平衡的影响。
