The gene polymorphisms of IL-8(-251T/A) and IP-10(-1596C/T) are associated with susceptibility and progression of type 2 diabetic retinopathy in northern Chinese population

Abstract

PurposeThe aim of the present study is to investigate the association of the polymorphism of two genes in CXC chemokine family, interleukin-8 (IL-8) and interferon-inducible protein 10 (IP-10), with both susceptibility and progression of DR in T2D population of northern China.Patients and methodsA total of 1043 eligible type 2 diabetic patients from Heilongjiang of northern China were recruited for this study. They were grouped into: with diabetic retinopathy (DR, 528 cases) and without diabetic retinopathy (DNR, 515 cases). Single nucleotide polymorphism (SNP) genotyping of IL-8(-251T/A) and IP-10(-1596C/T) was performed by polymerase chain reaction. Multivariate analysis and stepwise multiple logistic progression analysis were conducted to evaluate the association between gene SNP and DR susceptibility and progression. Pooled odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association among study groups.ResultsThe occurring of IL-8(-251) AA genotype was correlated with susceptibility (OR: 2.286, 95% CI: 1.382-3.782, P=0.001) and progression of high-risk proliferative diabetic retinopathy (PDR) (OR: 0.354, 95% CI: 0.162-0.770, P=0.009). Reversely, T allele of IP-10 (-1596) C/T was correlated with a reduced risk of DR (OR: 0.341, 95% CI: 0.249-0.466, P<0.001). However, gene polymorphisms of IL-8-251T/A and IP-10-1596C/T were not associated with diabetic macular edema (DME)(P>0.05).ConclusionsAA genotype of IL-8-251T/A was closely correlated to DR and high-risk proliferative diabetic retinopathy (PDR). -1596T allele of the IP-10 is a beneficial genotype for DR.

Identifying Genetic Risk Factors for Diabetic Macular Edema and the Response to Treatment

“…Dong et al [ 69 ] investigated a monocyte chemoattractant protein-1 ( MCP1 ) polymorphism in an Asian DM cohort, and while they observed a significant association with overall DR risk and proliferative DR, they found no association with severity of DME (mildDME = 207, moderateDME = 173, severeDME = 66). Another study by Dong et al [ 70 ] using the same cohort of patients as above [ 69 ], analyzed an association between DR susceptibility and polymorphisms in the CXC chemokine family genes, interleukin 8 ( IL8 or CXCL8 ; -251T>A) and interferon gamma-induced protein 10 ( IP10 or CXCL10 ; -1596C>T) but failed to observe a significant association in a subgroup analysis of DME patients. Finally, Upadhyay et al [ 71 ] studied the association between the sarcolemma-associated protein ( SLMAP ) gene polymorphism, rs17058639, and DR risk.…”

Порівняльна Оцінка Впливу Чинників Прогресування Діабетичної Ретинопатії На Показники Ліпідного Обміну При Метаболічному Синдромі

“…We are inclined to consider that at the 1 st stage of developing DRP hypertriglyceridemia takes part in the formation of endothelial dysfunction and provides idiosyncratic metabolic "hit" on rheological properties of blood and endothelium of vessels, contributing to the realization of the influence from such markers of endothelial damage and low-gradual inflammation as interleukin-8 [5,13], inhibitor of activator of plasminogen-1 [3], vascular cell adhesion molecule type 1 [7], which are actively produced in the body in case of obesity. Hypercholesterolemia and dyslipidemia (by cholesterol LDLP), seemingly may lead to further progression of endothelial dysfunction by the type of the "second wave" at later stages of DRP.…”

“…Thus prophylaxis of complication of diabetes mellitus (DM) should include further examination of other modifying or non-modifying risk factors. Contemporary references also testify to the importance of other factors including obstructive sleep apnea, nonalcoholic fatty liver disease, level of prolactin, homocysteine and hormones of adipose tissue of blood serum [1, 2, 9-12, 16, 17], genetic factors and endothelial dysfunction in development of DRP [5,13]. Considering the fact that the relative contribution of different factors to the risk of developing retinopathy remains uncertain, the search and study for new risk factors of development and progression of DRP and their modifying influence on components of the metabolic syndrome (MS) at T2DM remain actual.…”

Diabetic Retinopathy and Blindness: An Epidemiological Overview

“…The variability in the rate of progression to vision-threatening retinopathy and particularly in the response to treatment was noted from the onset of clinical and epidemiological studies in diabetic patients and has been attributed to the effect of genetic predisposition together with systemic and socioeconomic factors. Single-nucleotide polymorphisms [58][59][60] and genome-wide associations [61][62][63] have been investigated in patients with proliferative disease and macular edema, and the results so far are inconclusive mainly due to the size of the samples and the Diabetic Retinopathy and Blindness: An Epidemiological Overview DOI: http://dx.doi.org/10.5772/intechopen.88756 inclusion of cases with coexisting proliferations and edema in the cohorts. Detailed assessment in the polymorphisms of the VEGF gene revealed that some of them are related to higher susceptibility to severe retinopathy, but not to the outcome of ranibizumab intravitreal injections [64] in contrast to an earlier report on the response to bevacizumab [65].…”