Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
PLoS One. 2011 Jan 5;6(1):e15958. doi: 10.1371/journal.pone.0015958.
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.
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.
最近的一项研究报告称，FTO rs9939609 脂肪相关的 A 等位基因增加了血浆高敏 C 反应蛋白（hs-CRP）水平，而与肥胖无关。我们旨在研究该基因变异是否对丹麦男性在广泛的 BMI 范围内具有与肥胖无关的血浆 hs-CRP 和另外 10 种循环肥胖相关脂肪因子的影响。
方法/主要发现：在 1943 年至 1977 年间接受兵役检查的 362200 名年轻男性人群中，我们确定了两组人群：1）随机抽取的 1%样本和 2）所有肥胖男性（BMI = 31.0 kg/m2 ，均高于该人群第 99 百分位数）。在平均年龄为 49 岁（范围：39 至 65 岁）时，对 551 名男性进行了复查，其中包括 231 名肥胖男性，对其进行了基因分型和空腹循环炎症标志物 hs-CRP、IL-1β、IL-6、IL-10、IL-18、mip1α、mip1β、sTNFα-R1、TGF-β、TNF-α和瘦素的检测。患有已知疾病的男性被排除在检查之外。所有炎症标志物均经对数转换以近似正态分布。使用线性回归分析，以炎症标志物为响应变量，研究基因型与表型的关系。hs-CRP、瘦素与广泛的 BMI 之间存在显著正相关，但 FTO rs9939609 基因型之间的相关性没有显著差异。其他炎症标志物、FTO rs9939609 基因型或 BMI 之间均无显著相关性。
在代表广泛肥胖范围的健康中年男性队列中，未观察到 FTO rs9939609 A 等位基因对一系列炎症标志物的肥胖无关影响。
