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RESEARCH PRODUCT

FTO and INSIG2 Genotyping Combined with Metabolic and Anthropometric Phenotyping of Morbidly Obese Patients

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description

Obesity is a major health problem worldwide. Associations of obesity with common variants of the fat mass- and obesity-associated gene <i>(FTO) </i>and insulin-induced gene 2 <i>(INSIG2)</i> have been reported in various studies. We aimed to further investigate the association of 2 single nucleotide polymorphisms (SNPs), rs9939609 in <i>FTO</i> and rs7566605 in <i>INSIG2</i>, 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 <i>FTO</i> 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, <i>INSIG2</i> rs7566605 showed no association with obesity in our patients. Evaluation of metabolic data indicated associations between the high-risk <i>FTO </i>genotype (rs9939609_AA) and increased levels of serum glutamic oxaloacetic transaminase (GOT) and between the high-risk <i>INSIG2</i> genotype (rs7566605_CC) and lower waist-to-hip ratio and lower hemoglobin A1c (HbA1c) levels. Our results confirm an association of the <i>FTO </i>SNP with extreme obesity. However, we found no association of the potential obesity risk allele of <i>INSIG2</i> in our sample and thus cannot confirm an association of the <i>INSIG2</i> CC genotype with obesity. We identified an association between the high-risk <i>FTO</i> 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 <i>INSIG2</i> 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.