Burgdörfer E, Korenkov M, Jonas D, Weise D, Haaf T, Zechner U, Bartsch O
Institute of Human Genetics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
Mol Syndromol. 2013 Sep;4(6):273-9. doi: 10.1159/000353563. Epub 2013 Aug 14.
Obesity is a major health problem worldwide. Associations of obesity with common variants of the fat mass- and obesity-associated gene (FTO) and insulin-induced gene 2 (INSIG2) have been reported in various studies. We aimed to further investigate the association of 2 single nucleotide polymorphisms (SNPs), rs9939609 in FTO and rs7566605 in INSIG2, with body mass index (BMI) and other anthropometric and metabolic parameters in subjects with morbid obesity (BMI ≥40). SNPs rs9939609 and rs7566605 were genotyped in 124 unrelated morbidly obese patients (mean BMI = 50, range 40.1-77.1) from Mainz, Germany, and in 253 normal controls without a history of morbid obesity. Metabolic and anthropometric parameters were analyzed in 109 of the 124 patients, and associations with the genotype data were examined. The high-risk AA genotype for FTO rs9939609 was observed in 32.3% of patients versus 15.8% of controls (p = 0.0004) and was associated with an increased obesity risk [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.53-4.21]. The intermediate-risk AT genotype was found in patients and controls at similar frequencies (48.4 vs. 48.6%, OR = 0.99). The low-risk TT genotype for rs9939609 was found in 19.4% of patients (35.5% of controls; p = 0.0013) and was associated with a decreased risk for morbid obesity (OR = 0.43, CI = 0.26-0.73). In contrast, INSIG2 rs7566605 showed no association with obesity in our patients. Evaluation of metabolic data indicated associations between the high-risk FTO genotype (rs9939609_AA) and increased levels of serum glutamic oxaloacetic transaminase (GOT) and between the high-risk INSIG2 genotype (rs7566605_CC) and lower waist-to-hip ratio and lower hemoglobin A1c (HbA1c) levels. Our results confirm an association of the FTO SNP with extreme obesity. However, we found no association of the potential obesity risk allele of INSIG2 in our sample and thus cannot confirm an association of the INSIG2 CC genotype with obesity. We identified an association between the high-risk FTO genotype (rs9939609_AA) and higher GOT levels, which could possibly reflect the increased frequency of nonalcoholic steatohepatitis with obesity. We also detected associations of the high-risk INSIG2 genotype (rs7566605_CC) with lower waist-to-hip ratios and lower HbA1c levels, which may indicate amelioration of impaired glucose tolerance and type 2 diabetes for patients with this genotype after bariatric surgery.
肥胖是全球主要的健康问题。在各项研究中，已报道肥胖与脂肪量和肥胖相关基因（FTO）及胰岛素诱导基因2（INSIG2）的常见变异存在关联。我们旨在进一步研究FTO基因中的单核苷酸多态性（SNP）rs9939609和INSIG2基因中的rs7566605与病态肥胖（体重指数[BMI]≥40）受试者的BMI及其他人体测量和代谢参数之间的关联。对来自德国美因茨的124名无亲缘关系的病态肥胖患者（平均BMI = 50，范围40.1 - 77.1）和253名无病态肥胖病史的正常对照进行了SNP rs9939609和rs7566605基因分型。对124名患者中的109名进行了代谢和人体测量参数分析，并检验了其与基因型数据的关联。FTO rs9939609的高危AA基因型在32.3%的患者中出现，而在对照中为15.8%（p = 0.0004），且与肥胖风险增加相关[比值比（OR）= 2.54，95%置信区间（CI）= 1.53 - 4.21]。中等风险的AT基因型在患者和对照中的出现频率相似（48.4%对48.6%，OR = 0.99）。rs9939609的低危TT基因型在19.4%的患者中出现（对照中为35.5%；p = 0.0013），且与病态肥胖风险降低相关（OR = 0.43，CI = 0.26 - 0.73）。相比之下，INSIG2 rs7566605在我们的患者中与肥胖无关联。代谢数据分析表明，高危FTO基因型（rs9939609_AA）与血清谷氨酸草酰乙酸转氨酶（GOT）水平升高相关，高危INSIG2基因型（rs7566605_CC）与较低的腰臀比及较低的糖化血红蛋白A1c（HbA1c）水平相关。我们的结果证实了FTO SNP与极度肥胖之间的关联。然而，我们在样本中未发现INSIG2潜在肥胖风险等位基因的关联，因此无法证实INSIG2 CC基因型与肥胖的关联。我们发现高危FTO基因型（rs9939609_AA）与较高的GOT水平之间存在关联，这可能反映了肥胖患者中非酒精性脂肪性肝炎的发生率增加。我们还检测到高危INSIG2基因型（rs7566605_CC）与较低的腰臀比及较低的HbA1c水平之间的关联，这可能表明该基因型患者在减肥手术后糖耐量受损和2型糖尿病得到改善。
