Phenylethanolamine N-methyltransferase G-148A genetic variant and weight loss in obese women.

OBJECTIVE

To understand the impact of the phenylethanolamine N-methyltransferase (PNMT) G-148A gene and nutritional variables on weight loss in obese women.

RESEARCH METHODS AND PROCEDURES: One hundred forty-nine women, ages 45 to 65 with a body mass index of >30 kg/m(2), participated in a 6-month, open-label intervention that included sibutramine (15 mg/d) and a monthly health-education class. Anthropometric measurements, vital signs, food frequency, exercise log, medication compliance, and psychological and sociological questionnaires were completed each month. Genetic polymorphisms of PNMT were determined.

RESULTS

Univariate analysis of G/G, G/A, and A/A genotypes against tertiles of percentage of weight loss were significant at 3 but not at 6 months (Pearson chi(2): p < 0.006; homozygous/heterozygosity: p < 0.002, p < 0.253, and p < 0.122, respectively). A regression model that included the PNMT genetic variation and certain nutrition and exercise variables demonstrated that only the PNMT gene (beta = 0.360, SE 0.585, and p = 0.003) was statistically significant at 6 months, and the total calories (beta = -0.925, SE = 0.004, and p = 0.009), fiber intake (beta = 0.621, SE = 0.124, and p = 0.000), and PNMT (beta = 0.262, SE = 1.415, and p = 0.024) were significant.

DISCUSSION: The homozygosity/heterozygosity of the PNMT gene was highly predictive of significant weight loss with sibutramine during the first 3 months, which highlights the need for specific pharmacotherapy. The early weight-loss success of those subjects who were homozygous for PNMT may have motivated and selected those that would make further dietary changes, which then augmented their final weight loss.