Disproportionate vitamin A deficiency in pregnant women of specific ethnicities in the United States and ethnic differences in allele frequencies of polymorphisms of vitamin A-related genes
Authors: Suzuki Masako , Wang Tao , Garretto Diana J , Isasi Carmen R. , Cardoso Wellington V , Greally John M. , Quadro Loredana 
Published: January 2021

Abstract
BackgroundVitamin A is an essential micronutrient that plays critical roles in many biological functions of the body. The current national prevalence rate of vitamin A deficiency (VAD) in the United States is reported to be very low (<1%). However, our recent study in an urban city of the U. S. (the Bronx study) revealed that pregnant women in the Bronx have much higher proportions of VAD than the national prevalence rate. Given that Hispanics (56%) and non-Hispanic Blacks (29%) are the major racial and ethnic groups in the Bronx, we hypothesized that VAD could be more prevalent among pregnant women from specific ethnicities in the U.S. We therefore re-analyzed two independent datasets of serum retinol levels, i.e., the data from the the Bronx study and the National Health and Nutrition Examination Survey (NHANES). Moreover, as known polymorphisms have been associated with vitamin A status, we also assessed the differences of minor allele frequencies of these polymorphisms between ethnic groups in publicly available datasets, such as the Allele Frequency Aggregator (ALFA), the Population Architecture using Genomics and Epidemiology (PAGE), and the 1000 Genomes project. FindingsWe found that in both datasets of pregnant women non-Hispanic Black and Hispanic ethnicities have high proportions of VAD compared to non-Hispanic White pregnant women, and this VAD prevalence rate was much higher of the currently estimated national prevalence level. Interestingly, non-Hispanic Black pregnant women showed comparably high proportions of VAD in both datasets. However, pregnant women with Latin American/Afro-Caribbean ancestry in the Bronx dataset have strikingly high proportion of VAD compared to Latin American/Mexican ancestry in NHANES dataset (p= 1.973e-10, 95%CI 0.04 - 0.22, Fisher’s exact test). Furthermore, from the ALFA and the PAGE data analysis, we showed that the known single nucleotide polymorphism (SNP) located near the RBP4 gene (rs10882272) associated with lower serum retinol levels occurs at higher frequencies in Latin American/Afro-Caribbean ancestry and non-Hispanic Black/African populations compared to Latin American/Mexican ancestry and European populations. In addition, the analysis of minor allele frequency (MAF) of 39 previously reported SNPs associated with vitamin A metabolism showed significantly higher MAF variations between populations of different ancestries than that of randomly selected SNPs (p=0.030, permutation test with 1,000 iterations). ConclusionsWe confirmed that VAD rates in the pregnant women differ between different ethnicities, and that pregnant women in minority groups in the U.S. have much higher VAD rates than the estimated national prevalence level. Moreover, our analysis suggested that ethnic differences in allele frequencies of polymorphisms of vitamin A-related genes might contribute to the observed VAD rate differences. Further genome-wide association studies are needed to assess the influences of specific genetic variation and the different VAD status between different ethnic groups.