Genetic variants and physical activity interact to affect bone density in Hispanic children

Background: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study. Methods: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD. Results: We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p \u3c 0.05). Higher PRS was associated with a lower total body BMD (β = − 0.040 ± 0.009, p = 1.1 × 10− 5 ) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively). Discussion: The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study

Background: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

Abstract Background Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. Methods We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. Results All renal urate excretion measures were significantly heritable (p <2 × 10−6) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10−7. We observed a strong association (p < 8 × 10−8) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10−6, MAFs: 0.28–0.31). Conclusion For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations

Benchmarking green chemistry adoption by the Indian pharmaceutical supply chain

This paper provides the first benchmarking study of green chemistry (GC) adoption by the Indian pharmaceutical supply chain based on information from industry representatives leading such efforts. Results demonstrate that generic drug pharma and Active Pharmaceutical Ingredients (API) manufacturers in India exhibit significant interest and some advances in using GC principles. At the same time, majority (65%) of Indian companies rely on treatment and disposal of waste water instead of source reduction and one in five (20%) does not use any GC metrics. The study found that generic pharma is more advanced in adopting GC principles than API manufacturers. Regulatory risk and time pressures to deliver drugs were reported as the two most significant barriers for greater adoption of GC in India, while cost savings and environmental regulations were cited as the top two drivers. The paper concludes with some recommendations for advancing GC adoption in India

Genetic variants in ALDH1L1 and GLDC influence serine to glycine ratio in Hispanic children

Background: Glycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the10-formyltetrahydrofolate dehydrogenase (ALDH1L1) enzyme in serine to glycine conversion. Objectives: To determine the genomic influence on serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort. Methods: We performed a genome-wide association analysis for plasma serine, glycine, and serine-glycine ratio in SOLAR while accounting for non-independence among family members. Results: All three parameters were significantly heritable [h2 = 0.22-0.78, P \u3c 0.004]. The strongest associations for serine-glycine ratio were with single nucleotide polymorphisms (SNPs) in ALDH1L1 and glycine decarboxylase (GLDC) and for glycine with GLDC [P \u3c 3.5 × 10-8, effect sizes: 0.03-0.07]. No significant associations were found for serine. We also conducted a targeted genetic analysis with ALDH1L1 exonic SNPs and found significant association between serine-glycine ratio and rs2886059 [β (SE) = 0.68 (0.25), P = 0.006] and rs3796191 [β (SE) = 0.25 (0.08), P = 0.003], and glycine and rs3796191 [β (SE) = -0.08 (0.02), P = 0.0004]. These exonic SNPs were further associated with metabolic disease risk factors, mainly adiposity measures [P \u3c 0.006]. Significant genetic and phenotypic correlations were found for glycine and serine-glycine ratio with metabolic disease risk factors including adiposity, insulin sensitivity and inflammation-related phenotypes [ρg = -0.37 to 0.35, P \u3c 0.03, ρp = -0.19 to 0.13, P \u3c 0.006]. The significant genetic correlations indicate shared genetic effects among glycine, serine-glycine ratio, and adiposity and insulin sensitivity phenotypes. Conclusions: Our study suggests that ALDH1L1 and GLDC SNPs influence serine to glycine ratio and metabolic disease risk

Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India

PURPOSEAccurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non–high-income setting, with international input to evaluate the necessity of MTB in clinical practice.METHODSWe collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented.RESULTSSeventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases).CONCLUSIONThe discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders