Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia

Abstract

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explains the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia.

Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene

“…We performed a cis -eQTL analysis for the 5 genes within this TG-associated LD block using adipose RNA-seq samples (n=795) from the METSIM cohort and discovered that the lead SNP rs9949617 (i.e. the SNP with the strongest TG association signal 4 ) and its LD proxies are a cis -eQTL, regulating the expression of one regional gene, the transmembrane protein 241 ( TMEM241 ) (p=6.11x10 −07 –5.80x10 −04 ) (table 1). These results pass the Bonferroni correction for the 50 performed tests (10 SNPs tested for 5 regional genes; p<0.001) (table 1), and the 10 TG-associated SNPs did not regulate expression of any of the 4 other genes within the LD block (Bonferroni corrected p>0.05).…”

“…According to a recent survey, both the U.S. Hispanic men and women have higher levels of serum TGs than non-Hispanic whites or blacks 3 , a result consistently reported for the last two decades 4 . Recent studies utilizing Latino cohorts have successfully narrowed European lipid loci 5 .…”

Dyslipidemia in Mexico, a Call for Action

“…It has been observed that hypertriglyceridemia is more frequent in adults who live in metropolitan areas or in the central region of the country, without any influence being shown by educational level or socioeconomic status. It is well known that Hispanics have greater susceptibility to have hypertriglyceridemia 9 . For example, in the United States, the Hispanic population has a higher prevalence of hypertriglyceridemia (40.4% for men and 31.6% for women) compared to Caucasians and African-Americans.…”

Next-generation gene discovery for variants of large impact on lipid traits

“…For example, using novel lipid traits or underrepresented populations and allowing for pleiotropic effects have successfully identified novel loci [18,23,24▪,25–27]. Often, the most highly associated SNVs do not have a direct effect, but mark a region containing causal variation.…”