Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism.

High levels of plasma homocysteine are associated with an increased risk of many health conditions influenced by both environmental and genetic factors. The objective of this study was to provide the geographical distribution of folate pathway genetic polymorphisms in Mexico and the comparison with the reported frequencies in different continental populations. This study included the analysis of the genotypic frequencies of eight polymorphisms in genes of the folate/homocysteine metabolic pathway in 1,350 Mestizo and Amerindian subjects from different regions in Mexico and 836 individuals from European, African and Asian populations of the 1,000 Genomes Project. In Mexican Mestizo and Amerindian populations, the MTHFR C677T risk genotype (TT) was highly prevalent (frequency: 25 and 57 %, respectively). In Mestizos, the frequency showed clear regional variation related to ancestry; the Guerrero subpopulation with the highest Amerindian contribution had the highest TT frequency (33 %). The MTHFD1 G1958A AA risk genotype was also enriched in Mexican Mestizos and Amerindians (frequency: 34 and 58 %, respectively), whereas in African and Asian ancestry populations the frequency for AA was low (~4 %). All together risk genotypes showed regional differences, and Sonora had significantly different genetic frequencies compared with the other regions (P value <0.05). Our study illustrates differential geographical distribution of the risk variants in the folate/homocysteine metabolic pathway relative to ethnic background. This work supports that certain areas of the world have increased needs for folic acid and vitamin B supplementation, and this information needs to be considered in public health guidelines and eventually policies.

Hepatic amino acid-degrading enzyme expression is downregulated by natural and synthetic ligands of PPARα in rats.

Body nitrogen retention is dependent on the amount of dietary protein consumed, as well as the fat and carbohydrate content in the diet, due to the modulation of amino acid oxidation. PPARα is a transcription factor involved in the upregulation of the expression of enzymes of fatty acid oxidation. However, the role of putative PPARα response elements (PPREs) in the promoter of several amino acid-degrading enzymes (AADEs) is not known. The aim of this work was to study the effect of the synthetic ligand Wy 14643 and the natural ligands palmitate, oleate, and linoleate in rats fed graded concentrations of dietary protein (6, 20, or 50 g/100 g of total diet) on the expression of the AADEs histidase, serine dehydratase, and tyrosine aminotransferase. Thus, we fed male Wistar rats diets containing 6, 20, or 50% casein for 10 d. The results showed that addition of Wy 14643 to the diet significantly reduced the expression of the AADEs. Furthermore, the incubation of hepatocytes with natural ligands of PPARα or feeding rats with diets containing soybean oil, safflower oil, lard, or coconut oil as sources of dietary fat significantly repressed the expression of the AADEs. Gene reporter assays and mobility shift assays demonstrated that the PPRE located at -482 bp of the histidase gene actively bound PPARα in rat hepatocytes. These data indicate that PPARα ligands may reduce amino acid catabolism in rats.

Reconstructing Native American population history.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.