The folate hydrolase 1561C>T polymorphism is associated with depressive symptoms in Puerto Rican adults

Abstract

Objective: To examine the associations between variants of genes involved in the uptake, retention, and metabolism of folate and depressive symptoms and to analyze whether such associations are direct or through mediation by folate or homocysteine.

Methods: We performed a cross-sectional analysis of data from 976 Puerto Rican adults, aged 45 to 75 years, residing in the greater Boston area, Massachusetts. Twelve single nucleotide polymorphisms (SNPs) in genes involved in folate uptake, retention, and metabolism were investigated. These include FOLH1 (folate hydrolase), FPGS (folate polyglutamate synthase), GGH (γ-glutamyl hydrolase), MTHFR (methylenetetrahydrofolate reductase), MTR (methionine synthase), PCFT (proton-coupled folate transporter), and RFC1 (reduced folate carrier 1). The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms.

Results: The FOLH1 rs61886492 C>T (or 1561C>T) polymorphism was significantly associated with lower CES-D score (p = .0025) after adjusting for age, sex, population admixture, smoking, and educational attainment. Individuals with the TT and TC genotypes were 49% less likely (odds ratio = 0.51, 95% confidence interval = 0.29-0.89) to report mild depressive symptoms (CES-D score ≥16 and ≤26) and 64% less likely (odds ratio = 0.36, 95% confidence interval = 0.18-0.69) to report moderate to severe depressive symptoms (CES-D score >26), compared with those with the CC genotype. No significant mediation effects by plasma folate or homocysteine on the associations between this single nucleotide polymorphism and CES-D score were observed.

Conclusions: The FOLH1 1561C>T polymorphism may be associated with the risk of depressive symptoms.

Figures

Figure 1

The mediating effects of plasma folate (A) and homocysteine (B) on the association between folate hydrolase gene (FOLH1) rs61886492 C>T and Center for Epidemiologic Studies Depression Scale (CES-D) score. Genotypes were coded as 0 = CC and 1 = CT or TT. c = coefficient for total effect of FOLH1 rs61886492 genotype on CES-D score; c’ = coefficient for direct effect of FOLH1 rs61886492 genotype on CES-D score after control for the mediated effect of log-transformed folate (A), or log-transformed homocysteine (B). The bootstrapping coefficients (95% confidence interval) for the mediating effect of folate and homocysteine were −0.11 (−0.47, 0.03) and 0.03 (−0.05, 0.26), respectively. All coefficients are presented after the adjustment for age, sex, population admixture, smoking and educational level, using the Preacher and Hayes method (30). *p < .1; **p < .05; ***p < .01.