Fibroblast Growth Factor-23 (FGF-23) Levels Differ Across Populations by Degree of Industrialization.

CONTEXT: Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing phosphate intake may adversely impact health. However, population and clinical studies examining the link between phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which phosphate exposure may be homogenous. OBJECTIVE: The objective of the study was to contrast dietary phosphate intake, urinary measures of phosphate excretion, and FGF23 levels across populations that differ by the level of industrialization. DESIGN: This was a cross-sectional analysis of three populations. SETTING: The study was conducted in Maywood, Illinois; Mahé Island, Seychelles; and Kumasi, Ghana. PARTICIPANTS: Adults with African ancestry aged 25-45 years participated in the study. MAIN OUTCOME: FGF23 levels were measured. RESULTS: The mean age was 35.1 (6.3) years and 47.9% were male. Mean phosphate intake and fractional excretion of phosphate were significantly higher in the United States vs Ghana, whereas no significant difference in phosphate intake or fractional excretion of phosphate was noted between the United States and Seychelles for men or women. Overall, median FGF23 values were 57.41 RU/mL (interquartile range [IQR] 43.42, 75.09) in the United States, 42.49 RU/mL (IQR 33.06, 55.39) in Seychelles, and 33.32 RU/mL (IQR 24.83, 47.36) in Ghana. In the pooled sample, FGF23 levels were significantly and positively correlated with dietary phosphate intake (r = 0.11; P < .001) and the fractional excretion of phosphate (r = 0.13; P < .001) but not with plasma phosphate levels (r = -0.001; P = .8). Dietary phosphate intake was significantly and positively associated with the fractional excretion of phosphate (r = 0.23; P < .001). CONCLUSION: The distribution of FGF23 levels in a given population may be influenced by the level of industrialization, likely due to differences in access to foods preserved with phosphate additives.

Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs.

OBJECTIVE: To comprehensively assess the pharmacogenomic evidence of routinely used drugs for clinical utility. METHODS: Between January 2, 2011, and May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methods, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation. RESULTS: Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%), representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were recommended for clinical implementation using AGREE II, with mean ± SD overall quality scores of 5.18±0.91 (of 7.0; range, 3.67-7.0). Drug guidelines had highest mean ± SD scores in AGREE II domain 1 (Scope) (91.9±6.1 of 100) and moderate but still robust mean ± SD scores in domain 3 (Rigor) (73.1±11.1), domain 4 (Clarity) (67.8±12.5), and domain 5 (Applicability) (65.8±10.0). Clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Seven of the 9 most commonly prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information. CONCLUSION: Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.

Adoption of a clinical pharmacogenomics implementation program during outpatient care--initial results of the University of Chicago "1,200 Patients Project".

Pharmacogenomic testing is viewed as an integral part of precision medicine. To achieve this, we originated The 1,200 Patients Project which offers broad, preemptive pharmacogenomic testing to patients at our institution. We analyzed enrollment, genotype, and encounter-level data from the first year of implementation to assess utility of providing pharmacogenomic results. Results were delivered via a genomic prescribing system (GPS) in the form of traffic lights: green (favorable), yellow (caution), and red (high risk). Additional supporting information was provided as a virtual pharmacogenomic consult, including citation to relevant publications. Currently, 812 patients have participated, representing 90% of those approached; 608 have been successfully genotyped across a custom array. A total of 268 clinic encounters have occurred at which results were accessible via the GPS. At 86% of visits, physicians accessed the GPS, receiving 367 result signals for medications patients were taking: 57% green lights, 41% yellow lights, and 1.4% red lights. Physician click frequencies to obtain clinical details about alerts varied according to color severity (100% of red were clicked, 72% yellow, 20% green). For 85% of visits, clinical pharmacogenomic information was available for at least one drug the patient was taking, suggesting relevance of the delivered information. We successfully implemented an individualized health care model of preemptive pharmacogenomic testing, delivering results along with pharmacogenomic decision support. Patient interest was robust, physician adoption of information was high, and results were routinely utilized. Ongoing examination of a larger number of clinic encounters and inclusion of more physicians and patients is warranted.