|Ye, Xingwang -|
|Lai, Chao Qiang|
|Crott, Jimmy W. -|
|Troen, Aron M. -|
|Ordovas, Jose M. -|
|Tucker, Katherine L. -|
Submitted to: Psychosomatic Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 1, 2011
Publication Date: June 1, 2011
Citation: Ye, X., Lai, C., Crott, J., Troen, A., Ordovas, J., Tucker, K. 2011. The folate hydrolase 1561 C>T polymorphism is associated with depressive symptoms in Puerto Rican adults. Psychosomatic Medicine. 73(5):385-392. Interpretive Summary: Low plasma folate has been associated with depression. Genes involved in the metabolism of folate are identified and well-known. Population studies have further demonstrated that genetic variation in such genes is associated with plasma folate and homocysteine, biomarkers of cardiovascular disease and other age-related diseases. However, it is unclear whether such variants are also associated with depressive symptoms, directly or through an interaction with plasma folate or homocysteine. We genotyped 12 variants in genes involved in folate uptake, retention and metabolism in 979 Puerto Rican adults, aged 45-75 years, residing in the greater Boston area, MA. A depression score was used to measure depressive symptoms. We found that one of the genetic variants was significantly associated with the depression score. Individuals who carry T version of the variant have a low risk of becoming depressive when compared to those with two copies of C variant. Two additional variants in the same gene also show association with depressive symptoms. But we did not find any association between the other nine genetic variants and depression. In summary, we found genetic variants may modulate the risk of depression in adults.
Technical Abstract: Low plasma folate has been associated with depression. Variants of genes involved in the uptake, retention and metabolism of folate have been linked with plasma folate and homocysteine concentrations. It remains unclear whether such variants are also associated with depressive symptoms, directly or through an interaction with plasma folate or homocysteine. Twelve single nucleotide polymorphisms (SNPs) in genes involved in folate uptake, retention and metabolism were investigated in 979 Puerto Rican adults, aged 45-75 years, residing in the greater Boston area, MA. These genes include folate hydrolase (FOLH1), folate polyglutamate synthase (FPGS), r-glutamyl hydrolase (GGH), methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC1). The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms. The FOLH1 rs61886492 C >T SNP was significantly associated with lower CES-D score (P = 0.0012), after adjustment for covariates. Individuals with the TT and TC genotypes were 48% less likely (odds ratio: 95% confidence interval: 0.52: 0.31, 0.86) to have depressive symptomatology (CESD score greater than or equal to16 or self-reported use of antidepressant medication), compared to those with the CC genotype. The FOLH1 rs202712 C>T (P = 0. 049) and rs647370 G>A (P = 0.037) were also significantly associated with lower CES-D score. These associations were further confirmed in haplotype analysis. No significant interactions between these SNPs and plasma folate or homocysteine were observed in relation to CES-D score. Variations in the FOLH1 gene may modulate the risk of depressive symptoms in adults.