Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease

ObjectiveLow HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population.Approach and resultsA genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism.ConclusionsThis is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans

A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

We report a genome-wide association scan for facial features in B6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P valueso5 10 8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of B3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion

La relación hombre, ritual, naturaleza en una comunidad totonaca de la sierra norte de Puebla: la fiesta del Arcángel San Miguel en Tepango de Rodríguez

Tesis para optar por el grado de Licenciatura de Antropología Físic

El Tlacuache Núm. 616 (2014). 616 Año 13 (2014) abril. El Tlacuache

El habitar una identidad de género:los muxes del Istmo de Tehuantepec por Adrián Alfredo Flores Ezeta. - Deidades híbricas del cielo y de la tierra: Cosmovisión en torno al agua entre los totonacos de la Sierra Norte de Puebla por Gastón Macín Pérez

Cambio cultural, estilo de vida, adiposidad y niveles de glucosa en una comunidad totonaca de la Sierra Norte de Puebla

En el contexto de los estudios sobre los cambios en la alimentacion en las poblaciones indigenas de Mexico se realizo un estudio en una comunidad totonaca de la Sierra Norte de Puebla con dos objetivos: 1) estimar la prevalencia de hiperglucemia y obesidad en la población adulta (N = 229) mediante analisis bioquimicos y mediciones antropometricas y 2) aproximarse a las causas y formas en que ocurrieron los cambios en la alimentacion, actividad fisica y salud que explican el aumento de hiperglucemia y obesidad desde la perspectiva de los propios habitantes de la comunidad. En este estudio encontramos que 19.2 % de la muestra presenta obesidad (IMC ? 30) y 26.3 % trastorno de la glucosa en ayunas (glucosa serica ? 110 mg/dL). Al considerar que estos porcentajes son muy elevados para una comunidad rural, nos enfocamos en realizar un estudio etnografico en el cual se indago sobre los cambios en laalimentacion, actividad fisica, condiciones de vida y salud, y obtuvimos una detallada descripción de la dieta tradicional y actual, la cual aporta una perspectiva general de los elementos de cambio mas relevantes desde el punto de vista de los habitantes de la comunidad. Consideramos como factores cruciales en la modificacion de la dieta y la actividad fisica los cambios ocurridos a raíz de que se desarrollaron las vias de comunicacion, las cuales facilitaron la introduccion de nuevos alimentos que paulatinamente fueron desplazando a los productos locales. Sin embargo, esto no quiere decir que la dieta tradicional haya desaparecido por completo, pues aun se sigue basando en los alimentos cultivados en los huertos familiares, siendo la base principal el maiz producido de manera local

Selection scan in Native Americans of Mexico identifies FADS2 rs174616: Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions

The genetics of Mexico recapitulates Native American substructure and affects biomedical traits

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide