title: Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals.
abstract: OBJECTIVE
  The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population.
  
  
  METHODS
  A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP.
  
  
  RESULTS
  Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05).
  
  
  CONCLUSIONS
  LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.
authors.forename: Raquel de
authors.initials: Rd
authors.lastname: Oliveira
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.forename: Fabiana Dalla Vecchia
authors.initials: FD
authors.lastname: Genvigir
authors.forename: Marcelo Ferraz
authors.initials: MF
authors.lastname: Sampaio
authors.forename: Dikran
authors.initials: D
authors.lastname: Armaganijan
authors.forename: Marcia Martins Silveira
authors.initials: MM
authors.lastname: Bernik
authors.forename: Egidio Lima
authors.initials: EL
authors.lastname: Dorea
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.forename: Hamilton Massayuki
authors.initials: HM
authors.lastname: Hinuy
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001938:Brazil; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D054411:Receptors, Leptin / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D055105:Waist Circumference / Q000235:genetics
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D020738:Leptin; D054411:Receptors, Leptin; D005947:Glucose