Genetic Factors Contributing to Interindividual Variability of α-Tocopherol Levels in Subcutaneous Adipose Tissue among Healthy Adult Males.

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson's r = 0.24, 95% CI: [-0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.

The Interindividual Variability of Phytofluene Bioavailability is Associated with a Combination of Single Nucleotide Polymorphisms.

SCOPE: Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, ß-carotene or lycopene. Several studies suggest its bioavailability displays an elevated interindividual variability. The aim of this work is to investigate whether a combination of SNPs is associated with this variability. METHODS AND RESULTS: Thirty-seven healthy adult males consume a test meal that provides phytofluene from a tomato puree. Phytofluene concentrations are measured at fast and in chylomicrons at regular time intervals after meal intake. Identification of the combination of SNPs that best explained the interindividual variability of the phytofluene response is assessed by partial least squares regression. There is a large interindividual variability in the phytofluene response, with CV = 88%. Phytofluene bioavailability is positively correlated with fasting plasma phytofluene concentration (r = 0.57; p = 2 × 10-4 ). A robust partial least squares regression model comprising 14 SNPs near or within 11 genes (ABCA1-rs2487059, rs2515629, and rs4149316, APOC1-rs445925, CD36-rs3211881, ELOVL5-rs6941533, FABP1-rs10185660, FADS3-rs1000778, ISX-rs130461, and rs17748559, LIPC-rs17240713, LPL-rs7005359, LYPLAL1-rs1351472, SETD7-rs11936429) explains 51% (adjusted R2 ) of the interindividual variability in phytofluene bioavailability. CONCLUSIONS: This study reports a combination of SNPs that is associated with a significant part of the interindividual variability of phytofluene bioavailability in a healthy male adult population.

Genotype Effects on ß-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines.

BACKGROUND: The study aimed to identify 2 beta-carotene 15,15'-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. MATERIALS AND METHODS: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. RESULTS: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bear the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status, although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. CONCLUSION: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these 2 variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

Nutritional and genetic determinants of essential hypertension among adult respondents of the 2013 national nutrition survey, Philippines: a preliminary observational study.

Preventive strategies for hypertension and its sequelae require an understanding of their predisposing conditions and recognition of at-risk individuals. Several factors, both genetic and nongenetic, are influential, and likely vary in their effects across ethnicities. This study aimed to identify dietary, lifestyle-related differences and genetic variants associated with hypertension in Filipinos. The study included 147 adult Filipino respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Data on the socio-demographic profile and selected lifestyle factors were obtained via face-to-face interviews. Blood pressure, anthropometric and biochemical indicators of health were determined using standard procedures. Hypertension incidence was determined following American College of Cardiology/American Heart Association guideline. Genotyping utilized the customized Illumina Golden Gate genotyping array, with subsequent allele and genotypic association analytics. Genetic variant effects were adjusted to clinical parameters via logistic regression. Between those with and without hypertension, there was relatively higher intake of dietary protein, fat but not carbohydrates in the latter (P<.05). Of note, other established risk factors for hypertension, such as high lipid levels and fasting blood sugar, were consistently frequently seen among hypertensive respondents. Of the gene markers, 3 SNPs (rs10492602 of APOC [3' UTR], rs12721054 of CYP2C19 [exon] and rs4244285 [intergenic between PCDH17-DIAPH3 locus]) remained significant after multivariable logistic regression. The study highlights that both nutrition and genetic information may contribute to hypertension among Filipinos. This could guide public health initiatives to identify Filipinos susceptible to hypertension and recommend control strategies in lowering its morbidity rate.

Next Generation Sequencing of 502 Lifestyle and Nutrition related Genetic Polymorphisms reveals Independent Loci for Low Serum 25-hydroxyvitamin D Levels among Adult Respondents of the 2013 Philippine National Nutrition Survey.

OBJECTIVE: The study determined the relationship of serum vitamin D levels and 502 lifestyle and nutrition related genetic polymorphisms among adult respondents of the 2013 Philippine National Nutrition Survey (NNS). METHODOLOGY: A total of 1,160 adult respondents of the 2013 NNS living in the National Capital Region, Philippines were enrolled. Of the 1,160 sequenced samples, 833 passed the stringent quality control based on multiple parameters and were used for further analysis. Total serum 25-hydroxyvitamin D [25(OH)D] was determined using electro-chemiluminescence binding assay method. Genomic DNA was used for targeted next generation sequencing of 502 lifestyle and nutrition related polymorphisms. Analysis of variance, followed by Tukey post hoc analysis, was employed to compare 25(OH)D serum levels across genotypes. RESULTS: Of the study participants, 56% was classified as having low serum 25(OH)D. The lower serum 25(OH)D was observed in the following gene/genotypes: KNG1 rs11924390 T/T; ANKH rs2454873 G/G; NPFFR2 rs4129733 T/G; SH2B1 rs4788102 G/A; RAP1A rs494453 T/T and CRHBP rs7728378 T/C. These genes were previously associated to the risk of osteoporosis, obesity, type 2 diabetes mellitus, and stress response. CONCLUSION: Large-scale analysis of genes has shown great utility in the discovery of genetic factors that play a role in vitamin D nutrition. Interestingly, loci found in this Filipino population cohort were mostly independent from the canonical vitamin D synthesis and metabolism pathways. Understanding how genetic variations interact with nutrition and lifestyle may aid in the prevention of diseases through screening and identification of susceptible patients who would not benefit from regular supplementation with vitamin D because of genetic alterations and may also be used as basis for future development of functional food enriched with vitamin D.

Targeted next generation sequencing of the entire vitamin D receptor gene reveals polymorphisms correlated with vitamin D deficiency among older Filipino women with and without fragility fracture.

This study aimed to discover genetic variants in the entire 101 kB vitamin D receptor (VDR) gene for vitamin D deficiency in a group of postmenopausal Filipino women using targeted next generation sequencing (TNGS) approach in a case-control study design. A total of 50 women with and without osteoporotic fracture seen at the Philippine Orthopedic Center were included. Blood samples were collected for determination of serum vitamin D, calcium, phosphorus, glucose, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and as primary source for targeted VDR gene sequencing using the Ion Torrent Personal Genome Machine. The variant calling was based on the GATK best practice workflow and annotated using Annovar tool. A total of 1496 unique variants in the whole 101-kb VDR gene were identified. Novel sequence variations not registered in the dbSNP database were found among cases and controls at a rate of 23.1% and 16.6% of total discovered variants, respectively. One disease-associated enhancer showed statistically significant association to low serum 25-hydroxy vitamin D levels (Pearson chi-square P-value=0.009). The transcription factor binding site prediction program PROMO predicted the disruption of three transcription factor binding sites in this enhancer region. These findings show the power of TNGS in identifying sequence variations in a very large gene and the surprising results obtained in this study greatly expand the catalog of known VDR sequence variants that may represent an important clue in the emergence of vitamin D deficiency. Such information will also provide the additional guidance necessary toward a personalized nutritional advice to reach sufficient vitamin D status.