A potential sex dimorphism in the relationship between bitter taste and alcohol consumption.

BACKGROUND: Bitterness is an innate aversive taste important in detecting potentially toxic substances, including alcohol. However, bitter compounds exist in many foods and beverages, and can be desirable, such as in beer. TAS2R38 is a well-studied bitter taste receptor with common polymorphisms. Some have reported relationships between TAS2R38 genotypes, bitter taste phenotype and alcohol intake, however results have been mixed. These mixed results may be explained by the varying taste properties of different alcoholic beverages or a sex dimorphism in responses. METHODS: Bitter taste phenotype was assessed using PROP taste test and TAS2R38-P49A genotype was assessed by RFLP-PCR. Alcohol intake was assessed by food frequency questionnaire and classified by beverage type (beer, wine, spirits or mixed drinks). The relationships between bitter taste phenotype and carriage of the P allele of the TAS2R38-A49P gene and alcohol intake were assessed adjusted for and stratified by sex, and the interaction between taste and sex was evaluated. RESULTS: The relationship between alcohol intake and bitter taste phenotype varied by beverage type, with significant results for beer, spirits and mixed drinks, but not wine. When stratified, results varied by sex, and were only significant in males. Significant interactions were found for taster phenotype and sex (total alcohol intake and intake of beer and spirits). Results were similar for carriage of the TAS2R38-P49A P allele. CONCLUSIONS: Sex-specific interactions between bitter taste phenotype, TAS2R38 genotype and alcohol intake may explain variance in previous studies and may have implications for sex-specific disease risk and public health interventions.

Vitamin D Receptor Polymorphisms Relate to Risk of Adenomatous Polyps in a Sex-Specific Manner.

Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP.

Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker.

BACKGROUND: Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways. METHODS: We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case-control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n = 253) and a secondary cross-sectional cohort (over 65s; n = 649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender. CONCLUSIONS: Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines. GENERAL SIGNIFICANCE: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.

Vitamin D Receptor Genotype Modulates the Correlation between Vitamin D and Circulating Levels of let-7a/b and Vitamin D Intake in an Elderly Cohort.

BACKGROUND AND AIMS: Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships. We examined the correlations between vitamin D intake and circulating levels of the miRNAs let-7a/b, and the involvement of two common vitamin D receptor (VDR) polymorphisms, BsmI and ApaI. METHODS: Two hundred participants completed food frequency and supplement questionnaires, and were assayed for circulating let-7b expression by qPCR. Polymorphisms were detected using restriction fragment length polymorphism-PCR. RESULTS: let-7b expression negatively correlated with vitamin D intake (rs=-0.20, p=0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (rs=-0.27, p=0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (rs=+0.319, p=0.0497). These correlations were significantly different (z-score=2.64, p=0.0085). The correlation between vitamin D intake and let-7a was only significant in those without the ApaI restriction site. CONCLUSIONS: The correlation between vitamin D intake and let-7a/b expression in this cohort varies with VDR genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally.