ASOCIACIÓN DE ALGUNOS POLIMORFISMOS DE CITOCINAS EN LA RETINOPATÍA DIABÉTICA PROLIFERATIVA EN MESTIZOS MEXICANOS

Abstract

Type 2 diabetes (T2D) is a significantly growing public health problem worldwide, and 12 to 14 million people have been reported to be affected in Mexico. Diabetic Retinopathy (DR) is the most important ocular complication of diabetes and its prevalence goes from 28.8% in patients with less than 5 years of evolution up to 77.8% when evolution is over 15 years. DR is a progressive microangiopathy with capillary occlusion; when the capillaries degenerate, they do not perfuse the retina provoking vascular lesions and neovascularization. DR is classified according to severity in the following: Non-proliferative DR, which constitutes the initial phase with no serious damage to the vision; this complication does not progress in 80% of the cases. Proliferative DR (PDR) is characterized by the presence of microaneurysms and retinal neovascularization, fibrovascular tissue and vitreous and tractional hemorraghe, leading to retina deattachment. Different authors have claimed the participation of some cytokines in PDR development. IL1 seems to induce retinal cell apoptosis in the presence of hyperglycemia. The concentration of IL6 has been found increased in the vitrous and IL1 IL8 and TNF concentrations are elevated in the patients’ aqueous humor and in vitreous. TGF and TNF amplify inflammation of the eye. The aim of this study is to investigate the participation of the following cytokine polymorphisms in the development of PDR in Mexican Mestas patients: IL2, IL4, IL-6, IL-10, TNFα and INF. These polymorpysms are located within the promoter region, and may affect the expression level of the corresponding proteins. The present study included 212 T2D patients with no PDR as the control group, and 116 T2D patients with PDR, all of them were Mexican Mestizos attending the Retina Service of the Hospital para Evitar la Ceguera en México “Dr. Luis Sánchez Bulnes”. DNA was extracted from peripheral blood samples and IL2-330(G/T), IL4-590(C/T), IL6-174(G/C), IL10-1082(A/G), -819(T/C), -592(A/C), TNFα -238(A/G) y -308(A/G) e INF +874(A/T) polymorphisms were typed using TaqMan probes and a 7500 Real Time-PCR instrument (ABI). Allele and genotype frequencies were calculated for each polymorphism and their distribution was compared between controls and patients, using the SPSS7 software. Statistical significance was assessed by means of the Yates Chi2 test; OR and CI were calculated for the significantly deviated alleles or genotypes. The results show an association of IL2 -330(G/T) polymorphism with PDR. The frequency of the G allele, which is associated with high levels of IL2, was found increased in the PDR patients (OR=1.53, p=0.017); the frequency of the T allele was found decreased (OR=0.65, p=0.017). The IL2-330 TT genotype (OR=0.58, P=0.029), which is associated with low IL2 levels, and the IL4 -590(C/T) CC genotype (OR=0.042, p=0.53), that correlates with the synthesis of high levels of IL4, seem to confer protection to PDR development. The frequency of the AA genotype of INF +874 was found decreased in the patients, (OR=0.26, p=0.05). The IL6 -174(G/C), IL10 -1082(A/G), -819(T/C), -592(A/C), TNF -238(A/G) and -308(A/G) polymorphisms do not contribute to PDR etiopathogenesis. No interaction of any studied polymorphism and gender was detected. These results support the contribution of different elements of the cellular immune response in the inflammatory process in this complication, as suggested by other international studies. Nevertheless, these data should be confirmed in other independent series of patients, with a larger simple size and in other populations