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.