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.


METHODS
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.


CONCLUSIONS
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.
Peters
Warren R
WR
Loma Linda University, Center for Health Promotion, Loma Linda, California 92350, USA. wpeters@univ.llu.edu
MacMurry
James P
JP
Walker
Jennifer
J
Giese
Russell J
RJ
Comings
David E
DE
D000368:Aged; D001067:Appetite Depressants / Q000627:therapeutic use; D001521:Behavior Therapy; D001824:Body Constitution; D016022:Case-Control Studies; D003503:Cyclobutanes / Q000627:therapeutic use; D004032:Diet; D004043:Dietary Fiber / Q000008:administration & dosage; D002149:Energy Intake; D015914:Estrogen Replacement Therapy; D015444:Exercise; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000628:therapy; D010353:Patient Education as Topic; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D013997:Time Factors; D015431:Weight Loss / Q000235:genetics*
D001067:Appetite Depressants; D003503:Cyclobutanes; D004043:Dietary Fiber; D010625:Phenylethanolamine N-Methyltransferase; C058254:sibutramine