Association of IL-6 Gene (-174 and -572 G/C) Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Population

Abstract

Purpose: To investigate the association of interleukin (IL)-6 with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D) in a Chinese population. Methods: Two subtypes of the IL-6 promoter (-174 and -572 G/C) were genotyped in 215 T2D patients with PDR and 207 T2D patients with a normal retinal function (controls) using the PCR-RFLP method. The mRNA and protein expression of IL-6 was examined by real-time PCR. Results: T2D patients with PDR had a significantly higher frequency of IL-6 -174 GC (OR 0.58; 95% CI 0.34-0.99; p = 0.011) and IL-6 -572 GG (OR 0.53; 95% CI 0.24-1.14; p = 0.016) than T2D controls. The mRNA expressions of the rs1800795 GC and rs1800796 GG genotype were significantly increased compared to other cases (Fsig = 0.002, p = 0.001, respectively), followed by a relative increase in IL-6 in protein. Conclusions: IL-6 genotypes of rs1800795 GC and rs1800796 GG might point to a relatively high risk for T2D patients suffering from PDR in a Chinese population and they were associated with elevation of IL-6 expression in both mRNA and protein.

A transition of C to G (rs1800796) at promoter region of IL6 gene is associated with lowered risk of elevated blood glucose in rural Thais

“…Similarly, the rs1800796 IL6 polymorphism was postulated to affect the expression of interleukin 6 [11,17] which can initiate insulin resistance and eventually T2DM [3]. In addition, previous studies have produced related evidence [7,11,18]. Consistent with rs2794521 and rs1800796, the exchange of T to C allele at -1031 locus in the TNF gene was associated with T2DM [12][13].…”

“…The expansion of adipose tissue eventually activates chronic low-grade in ammation [3][4]. This results in increased secretion of an acute phase reactant protein, namely Creactive protein (CRP) [5][6], as well as in ammatory cytokines such as interleukin 6 (IL6) [6][7] and tumor necrosis factor alpha (TNF-α) [8], which are known to affect glucose homeostasis. Since the expression of cytokines and the degree of in ammation can be modulated by genetic polymorphisms, it is thought that the polymorphisms of genes encoding for these cytokines may also in uence the development of T2DM.…”

“…Polymorphisms located in promoter regions, including rs2794521 (-717 A/G) of CRP gene, -572 C/G (rs1800796) of IL6 gene and -1031 T/C (rs1799964) of TNF gene, have been associated with T2DM risk [7,[9][10][11][12][13]. Several studies demonstrated a notable in uence of the rs2794521 polymorphism on CRP secretion [14][15][16].…”

Connection between Il-6 -174g> C Polymorphism and Type II Diabetes

“…Серед останніх важливу роль відіграє інтерлейкін 6 (ІL-6) [7]. Численні дос-лідження довели роль цього цитокіну у патогенезі метаболічного синдрому та інсулінорезистентності [5,6]. Із зростанням рівня ІL-6 пов'язують розвиток ЦД2 та його ускладнень [7].…”

“…Одним з факторів, що визначають гіперпродукцію ІL-6, є поліморфізм в промотері гену IL-6 -в сайті -174 з однонуклеотид-ною заміною G/С [8]. На сьогодні є роботи, що демонструють зв'язок поліморфізму гену IL-6 у сайті -174G>C з розвитком ЦД2 та деяких його ускладнень [2,6]. Проте між іншим, даний вид полі-морфізму пов'язують з розвитком ожиріння, коро-нарної патології, раку молочної залози тощо [7].…”