Dataset Information

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

ABSTRACT:

Background

The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations.

Methods

A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression.

Results

FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings.

Conclusions

This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.

SUBMITTER: Villalobos-Comparan M

PROVIDER: S-EPMC5414298 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

Villalobos-Comparán Marisela M Antuna-Puente Bárbara B Villarreal-Molina María Teresa MT Canizales-Quinteros Samuel S Velázquez-Cruz Rafael R León-Mimila Paola P Villamil-Ramírez Hugo H González-Barrios Juan Antonio JA Merino-García José Luis JL Thompson-Bonilla María Rocío MR Jarquin Diego D Sánchez-Hernández Osvaldo Erik OE Rodríguez-Arellano Martha Eunice ME Posadas-Romero Carlos C Vargas-Alarcón Gilberto G Campos-Pérez Francisco F Quiterio Manuel M Salmerón-Castro Jorge J Carnevale Alessandra A Romero-Hidalgo Sandra S

BMC medical genetics 20170502 1

<h4>Background</h4>The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations.<h4>Methods</h4>A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obes ...[more]

PMID: 28464932

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Project description:BackgroundThe Asian origin of Native Americans is largely accepted. However uncertainties persist regarding the source population(s) within Asia, the divergence and arrival time(s) of the founder groups, the number of expansion events, and migration routes into the New World. mtDNA data, presented over the past two decades, have been used to suggest a single-migration model for which the Beringian land mass plays an important role.ResultsIn our analysis of 568 mitochondrial genomes, the coalescent age estimates of shared roots between Native American and Siberian-Asian lineages, calculated using two different mutation rates, are A4 (27.5 ± 6.8 kya/22.7 ± 7.4 kya), C1 (21.4 ± 2.7 kya/16.4 ± 1.5 kya), C4 (21.0 ± 4.6 kya/20.0 ± 6.4 kya), and D4e1 (24.1 ± 9.0 kya/17.9 ± 10.0 kya). The coalescent age estimates of pan-American haplogroups calculated using the same two mutation rates (A2:19.5 ± 1.3 kya/16.1 ± 1.5 kya, B2:20.8 ± 2.0 kya/18.1 ± 2.4 kya, C1:21.4 ± 2.7 kya/16.4 ± 1.5 kya and D1:17.2 ± 2.0 kya/14.9 ± 2.2 kya) and estimates of population expansions within America (~21-16 kya), support the pre-Clovis occupation of the New World. The phylogeography of sublineages within American haplogroups A2, B2, D1 and the C1b, C1c and C1d subhaplogroups of C1 are complex and largely specific to geographical North, Central and South America. However some sub-branches (B2b, C1b, C1c, C1d and D1f) already existed in American founder haplogroups before expansion into the America.ConclusionsOur results suggest that Native American founders diverged from their Siberian-Asian progenitors sometime during the last glacial maximum (LGM) and expanded into America soon after the LGM peak (~20-16 kya). The phylogeography of haplogroup C1 suggest that this American founder haplogroup differentiated in Siberia-Asia. The situation is less clear for haplogroup B2, however haplogroups A2 and D1 may have differentiated soon after the Native American founders divergence. A moderate population bottle neck in American founder populations just before the expansion most plausibly resulted in few founder types in America. The similar estimates of the diversity indices and Bayesian skyline analysis in North America, Central America and South America suggest almost simultaneous (~ 2.0 ky from South to North America) colonization of these geographical regions with rapid population expansion differentiating into more or less regional branches across the pan-American haplogroups.

Dataset Information

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

Background

Methods

Results

Conclusions

Publications

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

Similar Datasets

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