Identification of the start lost mutation in a morbidly obese Brazilian patient.

Background: gene () is an important regulator of food intake, body weight, and blood pressure. Mutations in are associated with the most common form of nonsyndromic monogenic obesity. variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the gene in a Brazilian cohort of severely obese adults and to investigate the phenotype-genotype correlation within variant carriers.

Methods: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0-11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12-21 years). The entire coding region of gene was screened by Sanger sequencing.

Results: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of . It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying variants had higher median of waist-hip ratio when compared to noncarriers (=0.048). These missense variants were also associated with hypertension (=0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers (=0.020 and =0.065, respectively). Val103Ile was also associated with hypertension (=0.003).

Conclusion: This study showed the prevalence of variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of on body fat distribution and blood pressure.