¹International Health Institute, Brown Medical School, Providence, Rhode Island, USA

²Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

³Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, USA

⁴Department of Health, American Samoa Government, Pago Pago, American Samoa

⁵Department of Health, Government of Samoa, Apia, Samoa

Correspondence to: S T McGarvey, International Health Institute, Box G-B497, Brown University, Providence, RI 02912, USA. E-mail: Stephen_McGarvey@brown.edu

^a†Current address: Genentech Inc., 1 DNA Way, South San Francisco, California, USA

Objectives: Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3' UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans.

Design: The study was designed to detect differences in the proportion of alleles at the six microsatellite markers between two groups of adult Samoans at the extremes of the longitudinal BMI distribution.

Subjects and Measurements: The 181 unrelated Samoan participants were 25-55 y of age, reported that all four grandparents were Samoan, resided in American Samoa (AS) or Samoa (S) and were without diagnosed hypertension or type 2 diabetes. Initial statistical analysis was based on ² tests of independence between marker allele frequencies and BMI status at each marker. The association of individual alleles with BMI status was tested by aggregating a marker's allelic data into a two-by-two contingency table and applying a two-tailed version of Fisher's exact test, with a Bonferroni correction to account for the multiple testing implicit in the procedure.

Results: There were no significant differences in allele frequencies at any of the markers between AS and S, as expected from our prior population genetic analyses. Only the LEP gene 3'-tetranucelotide repeat was associated (P<0.006) with BMI status. The distribution of the marker alleles at the LEP locus was significantly associated with the BMI groups (P<0.01), due to the low frequency of allele 226 in the high BMI group. The same pattern of association was found in sub-group analyses with low BMI individuals from AS and high BMI individuals from S.

Conclusion: These findings indicate that the leptin 3'-tetranucleotide repeat is associated with high BMI in adult Samoans, with allele 226 having a low frequency in the high BMI group.

International Journal of Obesity (2002) 26, 783-788. doi:10.1038/sj.ijo.0801996

Samoan; obesity; BMI; LEP locus; candidate genes