Association between the IL6 –174G/C SNP and maximally attained lung function
- B van den Borst1,2,
- N Y Souren1,3,4,
- M Gielen1,3,4,
- R J F Loos5,6,
- A D C Paulussen1,7,
- C Derom8,
- A M W J Schols1,2,
- M P A Zeegers1,3,4
- 1NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
- 2Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- 3Department of Complex Genetics, Cluster of Genetics and Cell Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
- 4Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK
- 5Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
- 6Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
- 7Department of Clinical Genetics, Cluster of Genetics and Cell Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
- 8Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
- Correspondence to B van den Borst, NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center+, PO Box 616, Maastricht 6200 MD, The Netherlands;
- Accepted 29 October 2009
- Published Online First 23 September 2010
Recently, He et al1 reported that the C allele of the interleukin 6 (IL6) –174G/C promoter polymorphism was associated with a rapid decline in forced expiratory volume in 1 s (FEV1) (≥3% predicted/year) and susceptibility to chronic obstructive pulmonary disease (COPD) in middle-aged smokers derived from three different cohorts.1 Alternatively, as also suggested by He et al in their discussion,1 we hypothesised that the IL6 –174G/C single nucleotide polymorphism (SNP) might not only affect the rate of lung function decline but also the maximally attainable value at around the age of 25. We investigated this hypothesis in young adults recruited from the East Flanders Prospective Twin Survey. Reproducible prebronchodilator lung function measurements according to international standards2 and IL6 –174G/C genotypes were available of 427 individuals (mean age 24.6±4.5 (SD), 232 women and 195 men). Mean FEV1, forced vital capacity (FVC) and FEV1/FVC ratio did not differ between current (n=131), former (n=33) and never smokers (n=263). The IL6 –174G/C SNP was genotyped using pyrosequencing technology. PCR conditions and primer sequences are listed in online table 1. Genotype frequencies of the IL6 –174G/C SNP were in accordance with Hardy–Weinberg equilibrium (p>0.05) (online Table 2). Data were analysed using the PROC MIXED method as previously described.3
In this sample of young adults, the IL6 –174G/C SNP showed no association with the FEV1, but the C allele of the IL6 –174G/C SNP was significantly associated with a lower FVC (p=0.03) and a higher FEV1/FVC ratio (p=0.003) under an additive mode of inheritance and independent of smoking status and birth weight (table 1).
Our results are in line with animal and in vitro studies consistently showing that IL-6 promotes lung morphogenesis, lung branching and surfactant protein A production during intrauterine lung development.4 Local IL-64 and IL-6 receptor5 expression has been described in the lungs during fetal development. Accordingly, our data suggest that the IL6 –174G/C SNP may alter local IL-6 expression levels, potentially interfering with normal lung maturation. Collectively, the study by He et al1 combined with these findings suggest that an interesting next step could be to investigate local IL-6 expression in the lungs in relation to the IL6 –174G/C SNP during the course of life: during intrauterine development, at young adult age, and in middle-aged non-smokers versus smokers with and without COPD.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.