Van Camp J K, Beckers S, Zegers D, Verrijken A, Van Gaal L F, Van Hul W
Department of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43, Edegem, 2650, Antwerp, Belgium.
Endocrine. 2014 Aug;46(3):477-84. doi: 10.1007/s12020-013-0088-7. Epub 2013 Nov 28.
Considering the role of sFRP5 in Wnt signalling, an important group of pathways regulating adipogenesis and inflammation, we performed a genetic association study on sFRP5 polymorphisms in a population of obese and lean individuals. Using information from the HapMap, two tagSNPs were identified in the sFRP5 gene region and genotyped on a population of 1,014 obese, non-diabetic individuals and 606 lean controls. We performed logistic and linear regression analysis including a wide variety of obesity parameters (BMI, waist circumference, height, WHR, fat mass, fat mass percentage and visceral, subcutaneous and total abdominal fat), in addition to OGTT and HOMA-IR values. We were able to show a significant association of sFRP5 with both total abdominal and subcutaneous fat. The association signal was only seen in obese males, and in this population, the minor allele of rs7072751 explains 1.8 % of variance in total abdominal fat. In addition, we saw a trend towards an association of rs10748709 with glucose metabolism. Although further research is necessary, we can conclude that sFRP5 is a significant regulator of fat development and distribution in obese males. We postulate that altered transcription factor binding on the rs7072751 surrounding sequence might play a role in the associations we found with both total abdominal and subcutaneous fat. In addition, although no conclusive evidence was found, our results indicate that sFRP5 genetic variation may affect glucose metabolism and it would be interesting to investigate this further.
鉴于分泌型卷曲相关蛋白5（sFRP5）在Wnt信号通路中的作用，Wnt信号通路是调节脂肪生成和炎症的重要通路组群，我们对肥胖个体和瘦个体群体中的sFRP5基因多态性进行了基因关联研究。利用国际人类基因组单体型图计划（HapMap）的信息，在sFRP5基因区域鉴定出两个标签单核苷酸多态性（tagSNP），并在1014名肥胖非糖尿病个体和606名瘦对照人群中进行基因分型。我们进行了逻辑回归和线性回归分析——除了口服葡萄糖耐量试验（OGTT）和胰岛素抵抗指数（HOMA-IR）值外，还纳入了多种肥胖参数（体重指数、腰围、身高、腰臀比、脂肪量、脂肪量百分比以及内脏、皮下和腹部总脂肪）。我们发现sFRP5与腹部总脂肪和皮下脂肪均存在显著关联。这种关联信号仅在肥胖男性中出现，在该群体中，rs7072751的次要等位基因解释了腹部总脂肪中1.8%的变异。此外，我们发现rs10748709与葡萄糖代谢存在关联趋势。尽管有必要进一步研究，但我们可以得出结论，sFRP5是肥胖男性脂肪发育和分布的重要调节因子。我们推测，转录因子与rs7072751周围序列结合的改变可能在我们所发现的与腹部总脂肪和皮下脂肪的关联中发挥作用。此外，尽管未找到确凿证据，但我们的结果表明sFRP5基因变异可能影响葡萄糖代谢，对此进一步研究将很有意义。
