Interethnic variation of the MMP-9 microsatellite in Amerindian and Mexican Mestizo populations: considerations for genetic association studies

Abstract

ABSTRACT. We studied the interethnic variation of the MMP-9 microsatellite in the Mestizo and Amerindian populations using R. Camacho-Mejorado et al. 2930©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 2929-2939 (2015) blood samples collected from 435 healthy unrelated individuals from the Central Valley of Mexico. DNA samples were genotyped using the -90 (CA) [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] repeat near the MMP transcriptional start site using capillary electrophoresis. Our data were compared with those from African, Asian, and European populations (N = 729). Both Mestizo and Amerindian populations were in Hardy-Weinberg equilibrium (P ≥ 0.05). However, strong genetic heterogeneity was found within the Mestizo population (94%, P ≤ 0.0001), which exhibited the highest frequency of Amerindian, African, and European alleles. Likewise, Amerindians showed 6.7% variation among populations (P ≤ 0.0001), suggesting a genetic substructure potentially associated with linguistic affiliations. These findings were corroborated with principal component and population differentiation analyses, which showed relative proximity among the Mestizos and their historical parental populations: Asian (F st ≥ 0.05), European (F st ≥ 0.09), and African (F st ≥ 0.02). Nevertheless, important differences were found between Mestizo and Nahuas (P ≤ 0.0001), and between Mestizo and Me'Phaas (P ≤ 0.0001). These findings highlight the importance of determining local-specific patterns to establish the population variability of MMP-9 and other polymorphic markers. Validation of candidate markers is critical to identifying risk factors; however, this depends on knowledge of population genetic variation, which increases the possibility of finding true causative variants. We also show that dissimilar ethnic backgrounds might lead to spurious associations. Our study provides useful considerations for greater accuracy and robustness in future genetic association studies.

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

“…Also, ethnic variations in the MMP9 allelic distribution have been reported; European populations exhibited the highest frequencies of the MMP9 Ã 14 allele; MMP9 Ã 21 is the most prominent one within Asian ancestry [63,64,68,71]. A prior study of our research group described a bimodal MMP9 distribution in the Mexican mestizos (alleles 14 and 21), whereas Native Americans presented similar distributions to Asian populations [29].…”

“…open sci. 6: 190775 obtained in Native and mixed ancestry populations have revealed undescribed risk polymorphisms besides interethnic variability in genes associated with clinical traits; these studies represent less than 4% of phenotype-genotype associations [28,29].…”

rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients

“…Nevertheless, 98% of the population are Mestizos, the descendants of the native Amerindians and immigrants from Europe and Africa who arrived in Mexican territory more than 500 years ago, during the period when Mexico was a Spanish colony. The remaining 2% of the Mexican population comprises other groups, mainly Amerindians (Camacho-Mejorado et al, 2015).…”