Association of PPARG2 Pro12Ala Variant with Larger Body Mass Index in Mestizo and Amerindian Populations of Mexico

Abstract

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.

The Genetic Diversity of the Americas

“…Nevertheless, it has been shown that there is a strong correlation between genetic estimates obtained with sets of ancestry-informative markers and those obtained with high-density data in samples from Ibero-America (37,82). A large variation has been reported in the individual estimates of ancestry within the predefined ancestry categories (19,24,82). Although potentially informative, it is problematic to contrast this variation across published studies because of the large differences in the number of markers examined and the sampling strategies used.…”

“…Rather, these studies have mostly concentrated on either the United States or Ibero-America (i.e., the former Spanish and Portuguese colonies) in isolation. This literature also shows different research approaches in that population genetic studies of the United States have usually examined separately the genetic diversity of European Americans, African Americans, and Hispanics (19,24). By contrast, studies of Ibero-American countries usually examine the extent of Native American, European, and African ancestry without reference to perceived ancestry labels (84,85,87).…”

PPARG-LYPLAL1 Multi-Allelic Combination Associated with Obesity and Overweight in Mexican Adolescent Females

“…22 Interestingly, Amerindian populations (Mazahuas and Nahuas) exhibited the highest frequencies of the Ala12 allele (25%), which was in agreement with previous studies in Yaquis, Mayas, and Triquis. 23 Conversely, European (≤10%) and African (≤1%) ethnicities showed lower frequencies of Ala12 than in Mestizos and Amerindians. 18 Therefore, it is likely that Amerindian lineages could contribute to the development of MD.…”

“…One possible interaction pathway between them could be energy balance, where both genes play a critical role. 23,25 It is possible that this interaction requires the participation of other molecular mediators (transcription factors) since recent research has suggested that LYPLAL1 is not directly regulated by PPARG. 25 Another possibility could be that LYPLAL1 may act as other lipases (lysophospholipase I) modulating the biological activity of different proteins, which in turn are regulated by PPARG.…”

“…Previous research supports our data concerning the interaction between PPARG-ADIPOQ, suggesting an epistatic effect between them. 8,23,28 In connection with LD presented in the different populations, two landscapes were found. The first one (LY-PLAL1 and MC4R) shows a real LD related to genetic distances (>1cM).…”