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Effect of the peroxisome proliferator activated receptor-γ gene Pro12Ala variant on body mass index: a meta-analysis
  1. S Masud,
  2. S Ye,
  3. on behalf of the SAS group
  1. The Human Genetics Division, University of Southampton School of Medicine, Southampton, UK
  1. Correspondence to:
 Dr Shu Ye
 Human Genetics Division, University of Southampton School of Medicine, Duthie Building (808), Southampton General Hospital, Southampton SO16 6YD, UK; shu.yesoton.ac.uk

https://doi.org/10.1136/jmg.40.10.773

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    Peroxisome proliferator activated receptor-γ (PPAR-γ) is a transcription factor abundantly expressed in adipocytes, and plays a key role in the regulation of adipocyte differentiation, lipid storage, glucose homeostasis, and blood pressure.1 Several rare, dominant negative mutations have been detected in three families with severe insulin resistance, diabetes, and hypertension,2 while a rare, gain of function mutation has been detected in four unrelated individuals with extreme obesity.3 In addition, a meta-analysis based on data from over 3000 individuals has shown that a common polymorphism in the PPAR-γ gene has an influence on individual susceptibility to type 2 diabetes.4–8 Taken together, these findings indicate that rare, severe mutations of the PPAR-γ gene may cause extreme metabolic syndrome in a small number of patients, while common, mild variants of this gene may contribute to the common, multifactorial forms of these disorders.

    Systematic screening of the PPAR-γ gene for sequence variants has identified two common polymorphisms.9–11 These are, respectively, a C→G substitution in exon B resulting in the conversion of proline to alanine at residue 12 of the PPAR-γ protein, and a synonymous C→T substitution at nucleotide position 161 in exon 6.9–11 In this study, we examined these genetic variants in relation to body mass index (BMI) in a large cohort of white British patients with coronary artery disease (CAD), a disease closely related to obesity, dyslipidaemia, diabetes, and hypertension.

    A number of previous studies have examined the Pro12Ala polymorphism in relation to BMI;12 however, the results of these studies were not totally consistent. The disparate findings may be partly attributed to insufficient power in some studies. In addition, it has been suggested that the Pro12Ala polymorphism has an effect on BMI in individuals with marked obesity, and that this effect is not apparent …

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