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. 2019 Dec 2;14(12):e0225030.
doi: 10.1371/journal.pone.0225030. eCollection 2019.

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

María Guadalupe Salas-Martínez  1   2 , Yolanda Saldaña-Alvarez  1 , Emilio J Cordova  1 , Diana Karen Mendiola-Soto  1 , Miguel A Cid-Soto  1 , Angélica Luckie-Duque  3 , Hermenegildo Vicenteño-Ayala  4 , Francisco Barajas-Olmos  1 , Cecilia Contreras-Cubas  1 , Humberto García-Ortiz  1 , Juan L Jiménez-Ruíz  1 , Federico Centeno-Cruz  1 , Angélica Martínez-Hernández  1 , Elvia C Mendoza-Caamal  5 , Elaheh Mirzaeicheshmeh  1 , Lorena Orozco  1   2
Affiliations

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

María Guadalupe Salas-Martínez et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Level of genetic differentiation (FST) for the five ADRB2 variants among MAs, MEZs and other continental populations (see also S2 Table).
Populations from the 1000 Genomes database were used. A) rs1042713A; B) rs1042714G; C) rs1042717A; D) rs1042718A; E) rs1042719C. The darkest blue indicates the lowest level of differentiation, whereas red indicates the highest FST value.
Fig 2
Fig 2
Linkage disequilibrium (LD) structure of ADRB2 SNPs in A) MAs and B) MEZs. The r2 value was calculated using Haploview software 4.2.
Fig 3
Fig 3. Pairwise FST values among the 31 MA ethnicities ordered geographically (see also S3 Table).
Calculations were performed with the five ADRB2 variants using GENEPOP software version 1.2. The darkest blue indicates the lowest level of differentiation, whereas red color indicates the highest FST value.
Fig 4
Fig 4. Geographic distribution of ADRB2 alleles in five regions among MAs and MEZs.
A) rs1042713A; B) rs1042714G; and C) tag SNP rs1042717A; North (N), Central East (CE), Central West (CW), South (S) and South East (SE). Striped States were not sampled because they are inhabited by neighboring indigenous included in this study. *States without indigenous population.
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This study was supported by the Consejo Nacional de Ciencia y Tecnología Mexico, (CONACyT) grant numbers: S008-2014-1-233970. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript