Interleukin-6 gene -174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis.
OBJECTIVE
To determine whether the interleukin (IL)6 -174 gene polymorphism may influence the development of subclinical atherosclerosis manifested by the presence of endothelial dysfunction in RA patients.


METHODS
311 patients (228 [73.3%] women; 243 [78.1%] rheumatoid factor positive) who fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March 1996 and December 2006 and 226 matched controls were included in this study. Between March and December 2007, a subgroup of 98 patients randomly selected was assessed for the presence of endothelial dysfunction. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism (rs1800795) in the promoter region at the position -174 of the IL6 gene using a TaqMan 5' allele discrimination assay.


RESULTS
No significant differences in the IL6 -174 allele or genotype frequency between RA patients and controls were found. However, RA patients homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction (flow-mediated endothelium-dependent vasodilatation-FMD%: 4.2 + or - 6.6) than those carrying the IL6 -174 GC (FMD%: 6.3 + or - 8.1) or IL6 -174 CC (FMD%: 6.0 + or - 3.3) genotypes. In this regard, significant differences were observed when FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes (FMD%: 6.3 + or - 4.6) (p=0.02).


CONCLUSIONS
Our results support a role of IL6 -174 gene polymorphism in the development of subclinical atherosclerosis in patients with RA.
Palomino-Morales
R
R
Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.
Gonzalez-Juanatey
C
C
Vazquez-Rodriguez
T R
TR
Miranda-Filloy
J A
JA
Llorca
J
J
Martin
J
J
Gonzalez-Gay
M A
MA
D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D016009:Chi-Square Distribution; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index
D015850:Interleukin-6