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Gene Are Associated with Severe Overweight among Obese Women1
Departments of Clinical Nutrition (R.V., K.S., M.U.) and Medicine (R.M., J.P., M.L.), University of Kuopio, 70211 Kuopio; and the Eating Disorder Unit, University Hospital of Helsinki (A.R.), 00250 Helsinki, Finland; the Division of Medical Genetics, University of Washington (S.S.D.), Seattle, Washington 98195-7360; and INSERM U-325, Institut Pasteur de Lille (J.A.), Lille, France
Address all correspondence and requests for reprints to: Raisa Valve, M.Sc., Department of Clinical Nutrition, University of Kuopio, 70211 Kuopio, Finland. E-mail: raisa.valve{at}uku.fi
Peroxisome proliferator-activated receptor-
(PPAR) is a nuclear
receptor that regulates adipocyte differentiation. Variations in the
PPAR gene may affect the function of the PPAR and, therefore,
body adipocity. We investigated the frequencies of the
Pro12Ala polymorphism in exon B and the silent CAC478CAT
polymorphism in exon 6 of the PPAR gene and their effects on body
weight, body composition, and energy expenditure in obese Finns. One
hundred and seventy obese subjects [29 men and 141 women; body mass
index (BMI), 35.7 ± 3.8 kg/m2; age, 43 ± 8 yr;
mean ± SD) participated in the study. The frequencies
of the Ala12 allele in exon B and CAT478 allele in exon 6
were not significantly different between the obese and population-based
control subjects (0.14 vs. 0.13 and 0.19
vs. 0.21, respectively). The polymorphisms were
associated with increased BMI [Pro12Pro, 34.5 ± 3.8;
Pro12Ala, 34.8 ± 3.1; Ala12Ala, 39.2
± 4.6 kg/m2 (P = 0.011); CAC478CAC,
34.5 ± 3.8; CAC478CAT, 34.5 ± 3.3; CAT478CAT, 37.7 ±
4.1 kg/m2 (P = 0.046)]. In addition,
the women with both Ala12Ala and CAT478CAT genotypes
(n = 5) were significantly more obese compared with the women
having both Pro12Pro and CAC478CAC genotypes (n = 85;
BMI, 40.6 ± 3.3 vs. 34.4 ± 3.9
kg/m2; P = 0.001), and they had
increased fat mass (46.8 ± 9.1 vs. 36.8 ±
7.5 kg; P = 0.005). In conclusion, the
Pro12Ala and CAC478CAT polymorphisms in the PPAR gene
are associated with severe overweight and increased fat mass among
obese women.
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