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.

The learning curve of lateral access lumbar interbody fusion in an Asian population: a prospective study.

PURPOSE: Lateral access lumbar interbody fusion (LLIF) is a minimally invasive technique that has an increasing popularity. It offers unique advantages and circumvents risk of certain serious complications encountered in other conventional spinal approaches. This study provides a statistical analysis defining the lateral access learning curve in the Asian population. METHODS: This prospective study included 32 consecutive patients who underwent LLIF from April 2012 to August 2014. The surgeries were performed by two senior spine surgeons and follow-up was conducted at 6 weeks, 3, 6, 9 months and 1 year post-operation. RESULTS: The breakpoint in operating time occurred at the 22nd level operated, from a mean of 71 min in the early phase group to a mean of 42 min in the steady state group. LLIF at L4/5 level is technically more demanding but technically feasible as competency is achieved. CONCLUSIONS: During the learning process, there was no compromise of perioperative or clinical outcomes. It should be feasibly incorporated into a spine surgeon's repertoire of procedures for the lumbar spine.