IL-6 gene polymorphisms and CAD risk: a meta-analysis

Abstract

The potential relationship between Interleukin-6 (IL-6) gene polymorphisms and coronary artery disease (CAD) has been widely investigated. However, study findings on the -174 G/C and -572 G/C variants remain inconsistent and somewhat controversial. The present meta-analysis was conducted in an attempt to provide a more robust synthesis conclusion. PubMed and Embase were used to search for all relevant studies published on or before May 22, 2012. A total of 19 studies were ultimately included in the analysis. Overall combined risk was calculated with fixed or random-effects models. Subgroup and sensitivity analyses were performed. Among the included studies, no statistically significant differences were found between controls and CAD cases for the G allele contrasts of the -174 G/C and -572 G/C polymorphisms. The co-dominant genetic model was evaluated for the -174 G/C polymorphism. A significant association was detected using GG versus CC (OR = 0.801, 95 % CI: [0.652, 0.983], P = 0.034). However, the association was not obviously in subgroup analysis by ethnicity. The recessive genetic model was evaluated for the -572 G/C polymorphism. The relationship between -572 G/C polymorphism and CAD risk was only found to be significant in Asian populations (random-effects: OR = 1.908, 95 % CI: [1.016, 3.581], P = 0.044) using GG versus GC+CC. No obvious publication bias was found by Begg's funnel plots and the Egger's linear regression test (P = 0.315 for -174 G/C polymorphism and P = 0.118 for -572 G/C polymorphism). Our study indicated that the association between the IL-6 gene and CAD risk was mild and moderate for the -174 G/C and -572 G/C polymorphisms. However, this relationship requires additional investigation through well-designed studies with larger sample sizes.

Genetic and environmental determinants of population variation in interleukin-6, its soluble receptor and C-reactive protein: Insights from identical and fraternal twins

“…That may help to explain why studies of the association between the -176C/G SNP and cardiovascular disease have been inconsistent (Brull et al, 2001; Burzotta et al, 2001; Lieb et al, 2004; Nauck et al, 2002). Similar concerns have also been raised about the predictive power of IL-6 related SNPs in meta-analyses of the literature on inflammatory disease (Dai et al, 2012; Di Bona et al, 2009; Lee et al, 2012; Nikolopoulos et al, 2008; Yang et al, 2012). …”

Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers

“…Phulukdaree et al30 reported the rs1800795 G allele association with the increased risk of CAD development in South African Indians. In a meta-analysis study conducted by Yang et al32 including an additional 19 studies, rs1800795 and rs1800796 were associated with the increased risk of CAD. Conversely, some other studies found inconsistent results.…”

IL-6 gene promoter polymorphisms and risk of coronary artery disease in a Chinese population

“…A previous study conducted in South Africa showed that the IL-6 174 G allele influences mRNA levels and protein expression in CAD, and reduced the risk of CAD, with an OR (95%CI) of 0.47 (0.23-0.95) (Phulukdaree et al, 2013). A meta-analysis focusing on the IL-6 174G/C and -572G/C variants indicated that the association between the IL-6 gene and CAD risk was mild and moderate for these polymorphisms (Yang et al, 2013). These results agree with those of our study.…”