Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population

Abstract

The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.

The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas

“…Samples and data handling. The samples included in this study belong to the MAIS cohort [9][10][11]60 collected between 2012 and 2018. The MAIS cohort recruited genomic and clinical data from 77 indigenous communities from 60 different ethnic groups for a total of 3200 individuals [9][10][11]60 .…”

“…The samples included in this study belong to the MAIS cohort [9][10][11]60 collected between 2012 and 2018. The MAIS cohort recruited genomic and clinical data from 77 indigenous communities from 60 different ethnic groups for a total of 3200 individuals [9][10][11]60 . All individuals were selfrecognized as Indigenous members of an ethnic group and had parents and grandparents born in the same community.…”

Brain radiotoxicity-related 15CAcBRT gene expression signature predicts survival prognosis of glioblastoma patients

“…We examined the distribution of the novel variants across protein sequence and 3D structure of E-RGs in a Mexican population (genomic data previously obtained by our group), 14 ( Supplementary Tables S6–S8 ). According to the structural analysis, 3D clusters containing at least three variants in spheres with 15-30 Å diameters were discovered in APOE, COMT, CYP1B1, MGMT, and POR ( Figure 3 ).…”

“…The proteins encoded by RGs were named radiotoxic proteins (RPs). Novel variants of R-SNVs identified utilizing prospectively collected data from Mexican population 14 were also included in our analysis (see Supplementary Materials and Methods ).…”

Alpha and beta adrenergic receptors modulate keratinocyte migration

“…Sexual dimorphism has been reported for B2AR responses [49][50][51], so confirming the observed results in keratinocytes derived from females will be important. The de-identified neonatal foreskins collected for the study do not provide any information regarding potential racial differences in responses, and this could be a factor to investigate especially in view of racial B2AR polymorphism differences [52][53][54][55].…”