GENETIC-VARIANTS OF THE HUMAN OBESITY (OB) GENE - ASSOCIATION WITH BODY-MASS INDEX IN YOUNG-WOMEN, PSYCHIATRIC-SYMPTOMS, AND INTERACTION WITH THE DOPAMINE D-2 RECEPTOR (DRD2) GENE

To examine the possible role of genetic variants of the OB gene in obe sity we examined alleles of a dinucleotide repeat polymorphism, D7S187 5, close to the gene, in a group of adult, non-Hispanic Caucasians, Th ere was a significant correlation with body mass index (BMI) at age 26 30 years for males and females combined (P = 0.04) and females only (P = 0.028). Because of the frequent association between obesity and psy chiatric symptoms all subjects were screened with the Symptom List 90 (SCL-90). There was a significant increase in scores for anxiety (P = 0.0005), depression (P = 0.003), and other behaviors for subjects homo zygous for the OB1875 <208-bp alleles. Analysis of covariance indicate d that this was directly related to the OB alleles and not secondary t o the presence of obesity. There was a significant association between the BMI at ages 16 to 40 and homozygosity for the OB1875 <208-bp alle les and/or the presence of the DRD2 Tag A1 allele for males and female s combined (P = 0.002 to 0.005), and for females alone (P = 0.0017 to 0.0005). For females alone these two genes accounted for up to 22.8% o f the variance of the BMI. These results are consistent with the polyg enic inheritance of obesity, the greater involvement of genetic factor s in women and younger individuals, and suggest that variants of the O B gene are causally involved not only in human obesity but its associa ted behavioral disorders.