A comparison of obesity candidate genes in the anabolic neuropeptide pathway in the Samoan and American Samoan populations.

摘要

Obesity is a significant public health problem with substantial morbidity and mortality costs, increasing at an alarming rate. The literature suggests that obesity is a complex genetic disorder, influenced by environmental factors. The Samoan Islands represent an isolated population that recently divided into two polities, American Samoa and the independent nation of Samoa. Although genetically similar, these two populations differ significantly in their prevalence of obesity and lifestyle. The American Samoans and Samoans have a very high rate of obesity, 84% in women and 78% in men in America Samoa; and 59% for women and 29% for men in Samoa. The American Samoans have taken on a modern lifestyle and diet while the Samoans remain traditional in their lifestyle and diet. This is the ideal population to conduct a candidate gene association study. The Samoans migrated from Southeast Asia, facing periods of feast and famine. The "thrifty genotype" (as proposed by James Neel) would allow the Samoan individuals with high fat storage and decreased metabolism to survive, and pass those genes on to the next generation. Therefore, a candidate gene study focusing on those thrifty genes might identify an association with obesity in the Samoan populations. The anabolic neuropeptide pathway functions to increase stores of body fat while decreasing metabolic rate, and eight key genes from this pathway were selected for this study. A group of 454 American Samoan and 536 Samoan individuals were genotyped for single nucleotide polymorphisms (SNPs) within each gene. Only the neuropeptide Y gene was significant on an allelic, genotypic and haplotypic basis. Resistin also showed statistical significance when the obese individuals were compared on the haplotype level. Multivariate regression analysis was used to include the plasma levels of insulin, glucose and leptin, as well as systolic and diastolic blood pressure and smoking. Insulin, glucose, leptin and diastolic blood pressure were all significant with various SNPs when intervening variables were taken into account. Differences in the genotypes of the candidate genes coupled with the variation in lifestyle between these two Samoan populations, may explain the difference in obesity levels and provide clues for further obesity research.