Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level on the acute inflammation and neovascularization stages of patients with Eales' disease.
OBJECTIVE
To evaluate the role of interleukin-6 (IL-6) in the inflammatory and proliferative stages of Eales' disease (ED) and to determine the influence of IL-6-174G/C polymorphism in the IL-6 and IL-6-regulated protein expression, as well as the development of ED.


METHODS
One hundred and twenty-one patients diagnosed with ED, 223 matched healthy controls, and 16 control patients with macular holes were recruited from the eastern Indian population. Serum and vitreous levels of IL-6 and vascular endothelial growth factors (VEGF) were measured by enzyme-linked immunosorbent assay. Serum levels of high-sensitivity C-reactive protein (hsCRP) were measured by enzyme immunoassay. Subjects were genotyped for the IL-6-174G/C polymorphism (rs1800795) by a custom TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays system.


RESULTS
Serum IL-6 (p<0.0001), hsCRP (p<0.0001), and VEGF (p=0.0031) levels were significantly higher in the inflammatory stage of ED than in healthy controls. Serum IL-6 also significantly correlated with hsCRP (Spearman's correlation coefficient; r=0.4992, p=0.0009), but not with VEGF in this stage in ED patients. At the proliferative stage of ED, significantly higher levels of vitreous IL-6 (p=<0.0001) and VEGF (p=<0.0001) were found compared with the vitreous of patients with macular holes. A significant correlation was observed between vitreous IL-6 and VEGF in ED patients (Spearman's correlation coefficient; r=0.5834, p=0.0087). A statistically significant association was found between the -174GG genotype (p=0.006) and occurrence of ED. Mean serum and vitreous concentrations of IL-6 were also higher in the subjects with the GG genotype than in those with the GC or CC genotype in this population.


CONCLUSIONS
IL-6 expression, regulated by the allelic distribution of -174 loci and the enhanced level of IL-6, modulates CRP and VEGF concentration depending respectively on the acute inflammatory stimulation at the initial stage and angiogenic stimulation at the advanced stage of ED.
Department of Biochemistry, Dr. B C Roy Post Graduate Institute of Basic Medical Education and Research (IPGME&R), Kolkata, India.
Aditi
A
Sen
Suman Kalyan
SK
Paine
Imran Hussain
IH
Chowdhury
Amrita
A
Mukherjee
Subhadip
S
Choudhuri
Avijit
A
Saha
Lakshmi Kanta
LK
Mandal
Basudev
B
Bhattacharya
D000208:Acute Disease; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis / Q000096:biosynthesis; D016022:Case-Control Studies; D016172:DNA Fingerprinting; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007194:India; D007249:Inflammation / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012167:Retinal Perforations / Q000235:genetics / Q000276:immunology; D031300:Retinal Vasculitis / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology; D014822:Vitreous Body / Q000737:chemistry / Q000276:immunology*
C508600:IL6 protein, human; D015850:Interleukin-6; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein