Metabolic syndrome is a cluster of risk factors for type 2 diabetes and cardiovascular disease. Multiple mechanisms, including genetic factors, may contribute to this condition. The Trp64Arg variant in the β3-adrenergic receptor has been associated with features of the metabolic syndrome (1). A relatively common gene variant, Pro12Ala of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) has been previously studied for association with obesity and type 2 diabetes (2,3).
The Parkataje Indians, from the Brazilian Amazon region, remained largely isolated. Recently, they underwent a rapid and intensive process of acculturation, with important changes in their lifestyle. Accompanying these changes, an increasing prevalence of obesity and other features of the metabolic syndrome have been observed. This study examines the relevance of the Trp64Arg mutation in the β3-adrenergic receptor gene and the Pro12Ala mutation in the PPARγ2 gene as a susceptibility factor to features of the metabolic syndrome in this population.
Participants were individuals aged ≥20 years; those with admixture and pregnant women were excluded. The study population comprised 85 (52 men and 33 women) individuals (mean age 41 ± 14.9 years). The degree of relatedness among the individuals was determined, and 37 nuclear families from six pedigrees were verified. Polygamy, including polyandry, occurs in this population. BMI, waist-to-hip ratio, systolic and diastolic blood pressures, and serum lipoproteins were studied. Fasting and 2-h blood samples were drawn for glucose and insulin measurements. Changes in body weight were analyzed in 80 individuals for a 3-year period. Genotypes were determined by PCR/restriction fragment-length polymorphism, as previously described (1,2).
A principal component analyses from the correlation matrix of the variables measured was performed. Statistical analyses (ANOVA and family-based association test) were done with the first two principal components because the measured variables are all related to the metabolic syndrome. The principal component, therefore, reflects the variance common to these variables and avoids corrections for multiple independent tests.
Obesity rates were higher in women than in men (27.2 vs. 3.8% at baseline, P = 0.006 and 45.2 vs. 16.3% at 3-year follow-up, P = 0.01), and for both sexes, there was an increase in these rates during the follow-up period (12.94 vs. 27.5%, P = 0.03). Diabetes was diagnosed in one individual, impaired glucose tolerance in another, and the remaining were classified as normal glucose tolerant according to World Health Organization criteria.
Frequencies of the β3-adrenergic receptor Arg and the PPARγ2 Ala variants were 0.33 and 0.31, respectively. These frequencies are in the Hardy-Weinberg equilibrium. The β3-adrenergic receptor Arg allele frequency (0.33) is much higher than those reported in other populations, except for Pima Indians (4). Similarly, the PPARγ2 Ala allele was more prevalent in the Parkateje Indians than in the other populations, whose frequency ranges from 0.12 among Caucasians to 0.01 in Chinese (5). ANOVA (with Welch’s correction) showed that the first principal component was heterogeneous among the genotypic classes of the PPARγ2 locus; the AlaAla genotype was different from the others (F = 3.51, P = 0.035). The β3-adrenergic receptor locus showed no differences among the genotypes. The FBAT analyses showed that the PPARγ2 locus presented a significant segregation distortion with the recessive model (P = 0.032) but not with the additive or dominant models.
Among the Parkateje Indians, the Pro12Ala variant in the PPARγ2 gene, but not the Trp64Arg variant in the β3-adrenergic receptor, was associated with features of the metabolic syndrome.
