Influences of the Common FTO rs9939609 Variant on Inflammatory Markers Throughout a Broad Range of Body Mass Index

BACKGROUND: A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m(2), all of whom were above the 99(th) percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively. CONCLUSION: No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.