Research article
IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study
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* Corresponding author: Dilyara G Yanbaeva d.yanbaeva@pul.unimaas.nl
1 Department of Respiratory Medicine, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Centre, Maastricht, The Netherlands
2 Department of Research, Development & Education, Centre for Integrated Rehabilitation of Organ failure (CIRO), Horn, The Netherlands
3 Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands
4 Department of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands
5 Methodology & Statistics Department, Maastricht University Medical Centre, Maastricht, the Netherlands
BMC Medical Genetics 2009, 10:23 doi:10.1186/1471-2350-10-23
Published: 9 March 2009Abstract
Background
Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.
The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).
Methods
Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers. Plasma levels of CRP, IL-6 and FG were measured in the total study group. Differences in haplotype distributions were tested using the global and haplotype-specific statistics.
Results
Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients. However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile). Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003). Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005). None of the genes were associated with COPD-related phenotypes.
Conclusion
Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation.