Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil.
OBJECTIVE
To investigate associations of polymorphisms in the LEP, LEPR and NPY genes with obesity-related traits in a Brazilian population of European descent.


METHODS
A total of 183 women and 153 men (mean body mass index (BMI), 26.1+/-4.8 kg/m(2)) were genotyped using the PCR-RFLP procedure for the LEP A19G, LEPR Gln223Arg, LEPR PRO1019pro and NPY Leu7Pro polymorphisms. Frequencies were compared among normal-weight and overweight plus obese groups with chi-square tests, mean BMI and waist circumference were compared among genotypes by t-tests and analysis of variance.


RESULTS
The genotype and allele frequencies of the LEPR Gln223Arg polymorphism were significantly different between normal-weight and overweight plus obese groups (P=0.013 and 0.009, respectively). Although there was no difference in the mean adjusted BMI among the three LEPRGln223Arg genotypes, a trend was observed for Arg/Arg individuals to have a higher mean BMI compared to Gln/Gln homozygotes, with heterozygote individuals presenting intermediate mean BMI between the two homozygote groups (ANOVA, P=0.063). However, in non-smokers, the LEPR Gln223Arg polymorphism showed a highly significant effect over BMI (P=0.009). When the analysis was restricted to premenopausal women, a highly significant effect of NPY was observed. Women bearing the Pro variant presented a lower BMI than wild-type homozygotes (P=0.001).


CONCLUSIONS
Our findings suggest that genetic variability in the leptin receptor and neuropeptide Y genes is implicated in body weight regulation, the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian population, especially in non-smokers, while the NPY Leu7Pro polymorphism was associated with BMI reduction in premenopausal women.
Mattevi
V S
VS
Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Zembrzuski
V M
VM
Hutz
M H
MH
D000328:Adult; D000704:Analysis of Variance; D001824:Body Constitution / Q000235:genetics / Q000502:physiology; D015992:Body Mass Index; D001938:Brazil; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000502:physiology; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics* / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D020738:Leptin