METABOLIC SYNDROME AND RELATED DISORDERS Volume 5, Number 3, 2007 © Mary Ann Liebert, Inc. Pp. 262–269 DOI: 10.1089/met.2006.0035 Family History of Diabetes, Acculturation, and the Metabolic Syndrome among Mexican Americans: Proyecto SALSA TAMARA NELSON, M.P.H. , 1 ANGELICA PEREZ, M.P.H. , 1 JOHN ALCARAZ, Ph.D. , 1 GREGORY TALAVERA, M.D., M.P.H., 1 and JEANETTE J MCCARTHY, Ph.D. 1 ABSTRACT Background: The purpose of this study was to examine effect modifiers of the relationship between family history of diabetes, a proxy for genetic predisposition, and the metabolic syn- drome. Methods: Subjects were a cross-sectional sample of 205 Mexican-Americans patients of the San Ysidro Health Center in San Diego County. Self-reported parental history of diabetes was examined as a risk factor for individual metabolic syndrome traits (hyperglycemia, hyper- tension, abdominal obesity, hypertriglyceridemia and low HDL-cholesterol) and a composite phenotype, defined both by standard modified National Cholesterol Education Program— Adult Treatment Panel III (NCEP-ATPIII) criteria and using principal components analysis, in age and sex-adjusted multiple logistic and linear regression models. Results: Family history of diabetes was most strongly associated with individual traits of hyperglycemia (P  .0002) and low HDL-C (P  .001) and conferred a significant increased odds of metabolic syndrome defined by both NCEP-ATPIII criteria (odds ratio 3.57, 95% con- fidence interval 1.82, 7.01; P.0002) and by principal components analysis (P  0.003). More- over, the family history association with metabolic syndrome was modified by number of years living in the United States (interaction P  .04). This same effect was not seen for dia- betes (P  .19). Conclusions: The results of our study support a common etiology for at least some compo- nents of the metabolic syndrome, especially hyperglycemia and low HDL-cholesterol, the ba- sis of which may be genetic. Moreover, the effect of genes on these traits may be modified by longer duration in the United States, supporting the concept of gene-environment inter- action in the development of the metabolic syndrome. INTRODUCTION T YPE 2 (NON-INSULIN-DEPENDENT) DIABETES MELLITUS (T2DM) has recently emerged as one of the most prevalent chronic diseases in developed countries. The pathological process preceding T2DM is characterized by a constel- lation of metabolic abnormalities, collectively referred to as the metabolic syndrome (MetS; Insulin Resistance Syndrome, Syndrome X) and includes a clustering of insulin resistance, abdominal obesity, dyslipidemia, and hyper- 1 School of Public Health, San Diego State University, San Diego, CA 262