In depth analysis of the association of FTO SNP (rs9939609) with expression of the classical phenotype of PCOS: a Sri Lankan study

Background: PCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. We previously identified FTO (rs9939609) as a susceptibility locus for PCOS among Sri Lankan women and also explored the role of kisspeptin. Associated factors of the FTO candidate gene among South Asians with PCOS are unknown. Methods: This study aimed to determine the association between FTO (rs9939609) polymorphism with clinical (BMI, acanthosis nigricans, hirsutism) and biochemical (serum kisspeptin and testosterone levels) characteristics of PCOS in a cohort of Sri Lankan women. Genetic and clinical data including serum kisspeptin and testosterone concentrations of our previously reported cases (n=55) and controls (n=110) were re-analyzed, specifically for an association with rs9939609 variant of FTO gene. Results: Logistic regression analysis (AA – OR=5.7, 95% CI=2.41-13.63, p<0.05) and genetic inheritance analysis (AA – OR=5.49, 95%CI=2.34-12.88, p<0.05) showed that FTO (rs9939609) polymorphism is significantly associated with PCOS and its metabolic manifestations. Serum testosterone was significantly higher in affected women with mutant genotypes (AA+AT) than the normal allele (TT) (p<0.05). Although serum kisspeptin was higher in subjects with PCOS and mutant alleles than controls, this difference was not significant (p>0.05). Conclusion: FTO gene variant rs9939609 is associated with hyperandrogenemia and metabolic manifestations of PCOS among women of Sri Lankan descent with the well-characterized phenotype. Serum kisspeptin and the FTO genotypes lack a significant association when adjusted for confounders.

In depth analysis of the association of FTO SNP (rs9939609) with expression of the classical phenotype of PCOS: a Sri Lankan study

Background: PCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. We previously identified FTO (rs9939609) as a susceptibility locus for PCOS among Sri Lankan women and also explored the role of kisspeptin. Associated factors of the FTO candidate gene among South Asians with PCOS are unknown. Methods: This study aimed to determine the association between FTO (rs9939609) polymorphism with clinical (BMI, acanthosis nigricans, hirsutism) and biochemical (serum kisspeptin and testosterone levels) characteristics of PCOS in a cohort of Sri Lankan women. Genetic and clinical data including serum kisspeptin and testosterone concentrations of our previously reported cases (n=55) and controls (n=110) were re-analyzed, specifically for an association with rs9939609 variant of FTO gene. Results: Logistic regression analysis (AA – OR=5.7, 95% CI=2.41-13.63, p<0.05) and genetic inheritance analysis (AA – OR=5.49, 95%CI=2.34-12.88, p<0.05) showed that FTO (rs9939609) polymorphism is significantly associated with PCOS and its metabolic manifestations. Serum testosterone was significantly higher in affected women with mutant genotypes (AA+AT) than the normal allele (TT) (p<0.05). Although serum kisspeptin was higher in subjects with PCOS and mutant alleles than controls, this difference was not significant (p>0.05). Conclusion: FTO gene variant rs9939609 is associated with hyperandrogenemia and metabolic manifestations of PCOS among women of Sri Lankan descent with the well-characterized phenotype. Serum kisspeptin and the FTO genotypes lack a significant association when adjusted for confounders.

In depth analysis of the association of FTO SNP (rs9939609) with expression of the classical phenotype of PCOS: a Sri Lankan study

Background: PCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. We previously identified FTO (rs9939609) as a susceptibility locus for PCOS among Sri Lankan women and also explored the role of kisspeptin. Associated factors of the FTO candidate gene among South Asians with PCOS are unknown. Methods: This study aimed to determine the association between FTO (rs9939609) polymorphism with clinical (BMI, acanthosis nigricans, hirsutism) and biochemical (serum kisspeptin and testosterone levels) characteristics of PCOS in a cohort of Sri Lankan women. Genetic and clinical data including serum kisspeptin and testosterone concentrations of our previously reported cases (n=55) and controls (n=110) were re-analyzed, specifically for an association with rs9939609 variant of FTO gene. Results: Logistic regression analysis (AA – OR=5.7, 95% CI=2.41-13.63, p<0.05) and genetic inheritance analysis (AA – OR=5.49, 95%CI=2.34-12.88, p<0.05) showed that FTO (rs9939609) polymorphism is significantly associated with PCOS and its metabolic manifestations. Serum testosterone was significantly higher in affected women with mutant genotypes (AA+AT) than the normal allele (TT) (p<0.05). Although serum kisspetin was higher in subjects with PCOS and mutant alleles than controls, this difference was not significant (p>0.05). Conclusion: FTO gene variant rs9939609 is associated with hyperandrogenemia and metabolic manifestations of PCOS among women of Sri Lankan descent with the well-characterized phenotype. Serum kisspeptin and the FTO genotypes lack a significant association when adjusted for confounders.

The Influence of FTO Polymorphism rs9939609 on Obesity, Some Clinical Features, and Disturbance of Carbohydrate Metabolism in Patients with Psoriasis

Background. Psoriasis is often accompanied by obesity, hyperlipidemia, diabetes, and metabolic syndrome as risk factors of cardiovascular conditions and premature mortality. Objective. The study was aimed at investigating whether psoriatic patients, who carry risk allele of obesity-related FTO gene, are more predisposed to obesity and metabolic disturbances and whether it influences the severity of psoriasis. Methods. 197 patients with psoriasis, representing Lower Silesia region of Poland, underwent physical examination and anthropometric measurements. Blood samples for biochemical and genetic analysis were collected. All patients were genotyped for FTO gene rs9939609 variant. Identification of SNP was conducted with the use of minisequencing method. Results. Around 63% of patients were carriers of at least one risk allele A and 20% were AA homozygotes. The A allele was associated with increased BMI and hip and waist circumferences. The carriers of risk allele had increased PASI and CRP values and tended to have an increased insulin concentration. Conclusion. Psoriatic patients, carriers of risk allele of FTO gene rs9939609, have an increased risk for more severe psoriasis and obesity and may develop obesity-induced insulin resistance.

Association of Fat Mass and Obesity-associated Gene (FTO) rs9939609 Variant with Early Onset Obesity among Bataknese and Chinese Children in Indonesia: A Case-control Study

BACKGROUND: Childhood obesity is associated with the risk of adult obesity and obesity-related chronic disease. The fat mass and obesity-associated gene (FTO) rs9939609 variant are of particular interest because of its association with body mass index (BMI) and obesity-related phenotypes. This study was conducted to investigate the association between FTO gene rs9939609 variant with early onset obesity among Bataknese and Chinese children in Medan, Sumatera Utara, Indonesia.METHODS: The case-control study was carried out at 10 elementary schools in Medan. There were 212 children recruited; 56 early onset obesity and 61 control Bataknese and 49 early onset obesity and 46 control Chinese children. This study included a questionnaire, anthropometric measurements, and blood test analysis. rs9939609 polymorphism genotyping was performed using RT-PCR. Logistic regression, odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of obesity associated with the risk alleles, p<0.05 was considered as statistically significant.RESULTS: This study found a significant association between rs9939609 and early onset obesity in Chinese children (p=0.01), but not in Bataknese. The frequency of AA genotype was lower in the early onset obesity than in the normal weight children, while an OR of 0.69 showed that this genotype may protect against weight gaining and that the TT genotype may predispose to obesity.CONCLUSION: We concluded that the FTO gene rs9939609 is associated with early onset obesity in Chinese ethnicity but not in Bataknese.KEYWORDS: pediatric obesity, FTO gene, rs9939609, polymorphism, Indonesia