Abstract
Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26–5.13, P = 0.01). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.
Highlights
Most diabetic patients, especially those with poor glycaemic control, develop diabetic retinopathy (DR), which remains the major cause of new-onset blindness among diabetic adults
Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype
Statistically significant difference was observed in the following parameters: duration of diabetes, insulin treatment, haemoglobin A1c (HbA1c), body mass index (BMI), and total LDL, HDL, and cholesterol levels
Summary
Especially those with poor glycaemic control, develop diabetic retinopathy (DR), which remains the major cause of new-onset blindness among diabetic adults. A member of the tumor necrosis factor (TNF) receptor superfamily glycoprotein osteoprotegerin (OPG), first identified in 1997, acts as an important regulatory molecule in the vasculature [4, 5]. It is expressed in the endothelial and smooth muscle cells, and it is modulated by proinflammatory cytokines and hormones, like insulin and TNF-α [6, 7]. OPG, known as osteoclastogenesis inhibitory factor (OCIF), was originally discovered as an inhibitor of bone resorption [8] This effect is due to binding and neutralisation of the receptor activator of the nuclear factor-κB ligand, thereby neutralizing its functions and negatively regulating osteoclast differentiation, activity, and survival resorption [5, 8]
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