Interactions Between Folate Intake and Genetic Predictors of Gene Expression Levels Associated with Colorectal Cancer Risk

Background Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (GxE) interactions and may provide information on the underlying biological pathway. Objective We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. Methods We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based GxE approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4,839 genes with available genetically predicted expression. We meta-analyzed results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. Results We found suggestive evidence of interaction with folate intake for genes including glutathione S-Transferase Alpha 1 (GSTA1; p=4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p=4.3E-4), and Aspartylglucosaminidase (AGA: p=4.5E-4). Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein. Conclusion We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk.

Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake

Past-oriented rumination and future-oriented worry are two aspects of perseverative negative thinking related to the neuroticism endophenotype and associated with depression and anxiety. Our present aim was to investigate the genomic background of these two aspects of perseverative negative thinking within separate groups of individuals with suboptimal versus optimal folate intake. We conducted a genome-wide association study in the UK Biobank database (n = 72,621) on the “rumination” and “worry” items of the Eysenck Personality Inventory Neuroticism scale in these separate groups. Optimal folate intake was related to lower worry, but unrelated to rumination. In contrast, genetic associations for worry did not implicate specific biological processes, while past-oriented rumination had a more specific genetic background, emphasizing its endophenotypic nature. Furthermore, biological pathways leading to rumination appeared to differ according to folate intake: purinergic signaling and circadian regulator gene ARNTL emerged in the whole sample, blastocyst development, DNA replication, and C-C chemokines in the suboptimal folate group, and prostaglandin response and K+ channel subunit gene KCNH3 in the optimal folate group. Our results point to possible benefits of folate in anxiety disorders, and to the importance of simultaneously taking into account genetic and environmental factors to determine personalized intervention in polygenic and multifactorial disorders.

Direct and Indirect Effects of Indoor Particulate Matter on Blood Indicators Related to Anemia

Exposure to indoor particulate matter (PM) is a potential risk factor that increases systemic inflammation and affects erythropoiesis. This study investigated the association between exposure to indoor PM and blood indicators related to anemia (BIRA) in housewives. Indoor PM and blood folate status are important factors in the risk of anemia. This was a housewife cohort study; we recruited 284 housewives in Seoul and Ulsan, Republic of Korea. Indoor exposure to PM2.5 and PM10 was measured by gravimetric analysis and sensors. We investigated the BIRA, such as hemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and mean corpuscular Hb concentration (MCHC). Statistical analysis was performed by multiple linear regression model and mediation analysis. The association between BIRA and PM was assessed by multiple linear regression models fitted by mediation analyses. The increase in the level of indoor PM2.5 was associated with a decrease in MCV (Beta coefficient (B): −0.069, Standard error (SE): 0.022) and MCH (B: −0.019, SE: 0.009) in gravimetric measurements. The increase in the level of indoor PM2.5 was associated with a decrease in Hb (B: −0.024, SE: 0.011), hematocrit (B: −0.059, SE: 0.033), and MCV (B: −0.081, SE: 0.037) and MCH (B: −0.037, SE: 0.012) in sensor measurements (PM2.5-Lag10). Further, we identified a serum folate-mediated PM effect. The indoor PM exposure was significantly associated with decreased Hb, MCV, and MCH in housewives. Taken together, our data show that exposure to indoor PM is a risk factor for anemia in housewives. Blood folate concentration can be a mediating factor in the effect of indoor PM on BIRA. Therefore, folate intake should be recommended to prevent anemia in housewives. Moreover, indoor PM exposure should be managed.

Assessment of Dietary Folate Intake and Pill Burden among Saudi Patients on Maintenance Hemodialysis

The aim of this study was to assess the adequacy of dietary folate intake and perceptions of pill burden among Saudi patients on maintenance hemodialysis (MHD). This was a cross-sectional study of adults (>18 years) on MHD (>3 months) attending the dialysis unit at King Saud University Medical City. Patient demographics, dietary folic acid intake, and perceptions of pill burden were collected. Fifty-four patients met the eligibility criteria, with a mean age of 57 ± 15.5 years. The majority were females (63%), and the most prevalent comorbidities were diabetes (43%) and hypertension (76%). The average number of medications/patients was 11 ± 2.9, and most patients were receiving folate supplementation (68.5%). The average dietary folate intake was 823 ± 530 mcg/day. Pill burden was bothersome, primarily due to taking too many medications (57%) while taking medications at the workplace was the least bothersome burden (17%). The reported high pill burden and adequate dietary folate intake by Saudi patients on MHD indicates that the omission of folate supplementation may be advantageous for this special population.

Consumption of dietary folate estimates and its implication for reproductive outcome among women of reproductive age in Kersa: cross-sectional survey

Background Dietary folate inadequacy is one the most common micronutrient deficiencies that cause neural tube defect (NTD) among infants in Sub-Saharan African countries. This study aims to determine the dietary intake of folate among women of reproductive age (WRA) of Kersa, Eastern Ethiopia. Methods A cross-sectional study took place among voluntary women that were selected from 1140 random households. Using a validated Food Frequency Questionnaire, participant’s weekly dietary intake history of Ethiopian foods and dietary folate intake was worked out. Statistical analysis was done at a 95% confidence interval. Modified Poisson regression was used to identify factors associated with dietary folate consumption. Result The estimated median usual intake of folate was 170 μg/d (IQR: 118.3; 252.2) and about 33% of WRA had low folate intake and 73.9% were at risk for folate inadequacy. From the reported food groups, Beans and Peas, Starchy staples, and Vitamin-A rich dark-green leafy vegetables were the top three ranked foods that contributed much of the dietary folate. The following conditions were statistically related to dietary folate inadequacy; women’s age, being in poor wealth index, low dietary diversity, having seasonal employment, and reliance on market food sources. Conclusions We found that women’s dietary intake of folate in Kersa is very low and cannot protect their offspring from the risk of having NTD. They could also potentially be predisposed to poor health outcomes. Diversifying and fortification of Ethiopian wheats and salts could decrease the burden of folate deficiency in the country.

Prevalence of inadequate intake of folate in the post-fortification era: data from the Brazilian National Dietary Surveys 2008-2009 and 2017-2018

The objectives were to compare the evolution of dietary folate intake, to estimate the prevalence of folate inadequacy (POFI) and the contribution of food groups to folate intake (dietary folate plus folic acid from fortified foods) in two post-fortification periods in the Brazilian population, according to life stages, geographic regions and per capita income. Population-based study including representative data from the National Dietary Survey - Brazilian Household Budget Surveys (NDS-HBS) 2008-2009 and 2017-2018, with a total of 32,749 (2008-2009) and 44,744 (2017-2018) individuals aged ≥10 years old, excluding pregnant and lactating women. The National Cancer Institute method was used to estimate the distributions of usual dietary folate intake. POFI was estimated according to Estimated Average Requirement (EAR) cut-off point method. After 10 years of the first NDS-HBS, POFI has increased in all sex-age groups, except for 10 to 13 y old. POFI among women of reproductive age was around 30% and 40% in 2008-2009 and 2017-2018, respectively. Higher POFI was observed in the North region. The top five food groups contributors to folate intake in Brazil were beans, breads, pasta & pizza, cakes & cookies and non-alcoholic beverages groups in both periods, differing in the rank order of the last two groups. Although being a country that has adopted mandatory folic acid flour fortification for almost two decades, increased POFI was observed in 2017-2018. This study brings significant scientific information, which can help understand folate dietary data in different contexts and consequently, guide the approach for public health fortification strategies.