Promoter Variable Number Tandem Repeat Polymorphism in a Dominican Population: Exploring Differences with Genetic Ancestry.

UNLABELLED

A variable number tandem repeat polymorphism has been described in the promoter (pVNTR) with three types of fragments: short (), medium (), and long (). The allele appears in strong linkage disequilibrium (LD) with the non-functional allele in populations of European ancestry, but independently of this, it also appears to reduce the level of CYP2C9 expression in human liver by up to 34%.

OBJECTIVES

This study, in a Dominican population with varying amounts of Western European, African, and Native American ancestry, aims primarily to determine the frequency of pVNTR, and the degree of LD of with Secondarily, it explores if the frequency of the allele is over- or under-represented in those with a greater component of African ancestry.

METHODS

A total of 193 healthy volunteers from the Dominican Republic participated in the study. The promoter region of was amplified and analyzed by capillary electrophoresis. Analyses of genotypes (, , , , and ) and genetic ancestry, estimated in 176 Dominican individuals by genotyping 90 ancestry informative markers, were previously performed in this population.

RESULTS

The frequencies of , and variants are 0.065, 0.896, and 0.039, respectively. LD between and was found (D' = 0.756, r = 0.702) to be weaker than in European populations.

CONCLUSIONS

Populations with a greater African ancestry component appear to present a lower-than-expected frequency of , as well as a lower tendency for this and alleles to be inherited together, as is common in Europeans. The present exploratory results warrant further research in vivo about the effects of in predicting activity. Its inclusion in testing panels for personalized drug therapy could be relevant in populations such as the Dominican, where the LD between and is low.