Yari Davood, Ehsanbakhsh Zohreh, Validad Mohammad-Hosein, Langroudi Farzaneh Hasanian
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
J Ophthalmic Vis Res. 2020 Aug 6;15(3):299-307. doi: 10.18502/jovr.v15i3.7448. eCollection 2020 Jul-Sep.
Keratoconus (KC) is a bilateral and noninflammatory disease, characterized by progressive thinning and anterior protrusion of the cornea and may result in severe visual impairment due to irregular astigmatism. Matrix metalloproteinases (MMP) are the main group of enzymes that degrade extracellular matrix proteins including collagens; Type IV collagen is found in the corneal stroma. MMP enzymatic activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). A decrease in TIMP-1 level is associated with the development of KC. In the present study, we investigated the impact of rs2228557 C/T and rs4898 C/T (X-chromosome) variants on the odds of KC development in a sample of Iranian population.
This case-control study was conducted on 140 patients with KC and 150 healthy control subjects. We used modified methods of Nested-PCR and ARMS-PCR in combination (Nested-ARMS-PCR) and confirmed their validity with RFLP-PCR.
Significant differences were noticed between KC patients and healthy individuals regarding the genotype TY or T allele frequencies of rs4898 in the male subjects (OR = 0.43, 95%CI: 0.20-0.92, = 0.03), whereas no significant differences were identified in the female subjects (OR = 1.07, 95%CI: 0.52-2.20, = 0.85). The rs2228557, T allele was associated with KC (OR = 0.69, 95% CI: 0.50-0.97, = 0.035).
In the rs2228557 variant, T allele acts as a protective factor from the disease and decreases the risk of KC compared with the C allele. Also, in our investigation about rs4898, we found that TY genotype or T allele decreased the risk of KC compared with the C allele in males and was a protective factor for KC in our population.
圆锥角膜（KC）是一种双侧性非炎症性疾病，其特征为角膜进行性变薄和前突，可能因不规则散光导致严重视力损害。基质金属蛋白酶（MMP）是降解包括胶原蛋白在内的细胞外基质蛋白的主要酶类；IV型胶原存在于角膜基质中。MMP的酶活性受金属蛋白酶组织抑制剂-1（TIMP-1）抑制。TIMP-1水平降低与KC的发生有关。在本研究中，我们调查了rs2228557 C/T和rs4898 C/T（X染色体）变异对伊朗人群样本中KC发生几率的影响。
本病例对照研究对140例KC患者和150名健康对照者进行。我们联合使用改良的巢式PCR和扩增阻滞突变系统PCR（巢式-ARMS-PCR），并通过限制性片段长度多态性PCR（RFLP-PCR）确认其有效性。
在男性受试者中，KC患者与健康个体在rs4898的基因型TY或T等位基因频率方面存在显著差异（OR = 0.43，95%CI：0.20 - 0.92，P = 0.03），而在女性受试者中未发现显著差异（OR = 1.07，95%CI：0.52 - 2.20，P = 0.85）。rs2228557的T等位基因与KC相关（OR = 0.69，95%CI：0.50 - 0.97，P = 0.035）。
在rs2228557变异中，与C等位基因相比，T等位基因起到疾病保护因子的作用，降低了KC风险。此外，在我们对rs4898的研究中，我们发现与C等位基因相比，TY基因型或T等位基因在男性中降低了KC风险，并且在我们的人群中是KC的保护因子。
