The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age

Background: Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common.

Objective: We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia.

Methods: Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences.

Results: Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n = 53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n = 475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P < 0.001).

Conclusions: Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375.

Keywords: Cambodia; EGRac; hemoglobin; hemoglobinopathy; riboflavin; women.