Early-onset high myopia (EoHM) is a disease that causes a spherical refraction error of ≥−6 diopters before 10 years of age, with potential multiple ocular complications. In this article, we report a clinical and genetic study of 43 families with EoHM recruited in our center. A complete ophthalmological evaluation was performed, and a sample of peripheral blood was obtained from proband and family members. DNA was analyzed using a customized next-generation sequencing panel that included 419 genes related to ophthalmological disorders with a suspected genetic cause, and genes related to EoHM pathogenesis. We detected pathogenic and likely pathogenic variants in 23.9% of the families and detected variants of unknown significance in 76.1%. Of these, 5.7% were found in genes related to non-syndromic EoHM, 48.6% in genes associated with inherited retinal dystrophies that can include a syndromic phenotype, and 45.7% in genes that are not directly related to EoHM or retinal dystrophy. We found no candidate genes in 23% of the patients, which suggests that further studies are needed. We propose a systematic genetic analysis for patients with EoHM because it helps with follow-up, prognosis and genetic counseling.

High myopia is the most severe and pathological form of myopia. It occurs when the spherical refractive error exceeds –6.00 spherical diopters (SDs) or the axial length (AL) of the eye is greater than 26 mm. This article focuses on early-onset high myopia, an increasingly common condition that affects children under 10 years of age and can lead to other serious ocular pathologies. Through the genetic analysis of 21 families with early-onset high myopia, this study seeks to contribute to a better understanding of the role of genetics in this disease and to propose candidate genes. Whole-exome sequencing studies with a panel of genes known to be involved in the pathology were performed in families with inconclusive results: 3% of the variants found were classified as pathogenic, 6% were likely pathogenic and the remaining 91% were variants of uncertain significance. Most of the families in this study were found to have alterations in several of the proposed genes. This suggests a polygenic inheritance of the pathology due to the cumulative effect of the alterations. Further studies are needed to validate and confirm the role of these alterations in the development of early-onset high myopia and its polygenic inheritance.

Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e., pharmacogenes) could affect their pharmacokinetic processes altering their drug exposure, efficacy, and toxicity. The main objective of this study was to investigate the effects of variants in pharmacogenes on the pharmacokinetics of tadalafil and finasteride. An exploratory candidate gene study involving 120 variants in 33 genes was performed with 66 male healthy volunteers from two bioequivalence clinical trials after administration of tadalafil/finasteride 5 mg/5 mg under fed or fasting conditions. Afterwards, a confirmatory study was conducted with 189 male and female volunteers receiving tadalafil 20 mg formulations in seven additional bioequivalence clinical trials. Regarding tadalafil, fed volunteers showed higher area in the time-concentration curve (AUC_∞), maximum plasma concentration (C_max), and time to reach C_max (t_max) compared to fasting volunteers; male volunteers also showed higher AUC_∞ and C_max compared to female volunteers. Furthermore, fed volunteers presented higher finasteride AUC_∞, C_max and t_max compared to fasting individuals. Variants in ABCC3, CYP1A2, CES1, NUDT15, SLC22A1/A2 and UGT2B10 were nominally associated with pharmacokinetic variation in tadalafil and/or finasteride but did not remain significant after correction for multiple comparisons. Genetic variation did not demonstrate to clinically impact on the pharmacokinetics of finasteride and tadalafil; however, additional studies with larger sample sizes are needed to assess the effect of rare variants, such as CYP3A4*20 or *22, on tadalafil and finasteride pharmacokinetics.

Background: Psoriasis is a skin disease characterized by the presence of erythematous, scaly plaques on the extensor surfaces of the body. Treatment varies according to the stage of the disease, with the most severe cases being treated with biologic treatments that differ in efficacy and persistence over time. This study aimed to evaluate the 10-year persistence of biologic drugs (adalimumab, etanercept, infliximab and ustekinumab) in the treatment of moderate-to-severe plaque psoriasis. Methods: A total of 143 patients (61 women and 82 men) were evaluated; data were collected from the electronic clinical history, and statistical analysis was performed using the SPSS program. In addition, 115 of them were genotyped in a previous study for 173 immune system genetic polymorphisms. Results: The persistence of biologic drugs at 10 years was 25.9% (95% CI: 17.2–34.5%). Adalimumab was the most persistent drug (41.5%), followed by ustekinumab (34.8%), infliximab (28%) and etanercept (9.3%). The main reason for discontinuation was insufficient efficacy (51%). Adalimumab allowed an increase in the dosing interval in 82.4% of patients who persisted and ustekinumab allowed an increase in 37.5%. The 10-year persistence was related to sex (higher in men, p < 0.001), biologic drug (p = 0.002) and polymorphisms in LMO4 (rs983332) (p = 0.014) and IL20RA (rs1167846) (p = 0.013). Conclusion: The results show that 25% of psoriasis patients treated with first-line biologics persisted at 10 years.

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the ABCG2 and SLCO1B1 genes to minimize ADRs and improve treatment efficacy. Despite these adjustments, some patients still experience ADRs. So, we performed a candidate gene study to better understand the pharmacogenetics of rosuvastatin. This study included 119 healthy volunteers who participated in three bioequivalence trials of rosuvastatin alone or in combination with ezetimibe at the Clinical Trials Unit of the Hospital Universitario de La Princesa (UECHUP). Participants were genotyped using a custom OpenArray from ThermoFisher that assessed 124 variants in 38 genes associated with drug metabolism and transport. No significant differences were observed according to sex or biogeographic origin. A significant increase in t_1/2 (p_multivariate(p_mv) = 0.013) was observed in the rosuvastatin plus ezetimibe trial compared with the rosuvastatin alone trials. Genetic analysis showed that decreased (DF) and poor function (PF) volunteers for the ABCG2 transporter had higher AUC_∞/DW (adjusted dose/weight), AUC_72h/DW and C_max/DW compared to normal function (NF) volunteers (p_mv< 0.001). DF and PF volunteers for SLCO1B1 showed an increase in AUC_72h/DW (p_mv = 0.020) compared to increased (IF) and NF individuals. Results for ABCG2 and SLCO1B1 were consistent with the existing literature. In addition, AUC_∞/DW, AUC_72h/DW and C_max/DW were increased in intermediate (IA) and poor (PA) NAT2 acetylators (p_mv = 0.001, p_mv< 0.001, p_mv< 0.001, respectively) compared to rapid acetylators (RA), which could be associated through a secondary pathway that was previously unknown.

Rosuvastatin has become a good choice in the statin group because it has shown greater efficacy in reducing lipid levels than other statins, allowing patients to reach their therapeutic goal more quickly. To date, research has shown a broad relationship between the kinetics and efficacy of this drug and the phenotype of two transporters, OATP1B1 and BCRP, encoded by SLCO1B1 and ABCG2 genes. However, there are many other genes whose variation may also affect the treatment. To conduct a systematic review including all information on the kinetics, measured by AUC and C_max parameters; efficacy, by reduction in lipid levels and carotid intima-media thickness; and safety of rosuvastatin, by the occurrence of adverse events. A search of the published literature was conducted in PubMed using the term "rosuvastatin AND pharmacogenetics" (PROSPERO code: CRD420251041953). A total of 37 articles were included, investigating 40 genes. The importance of ABCG2 in drug kinetics and efficacy and of SLCO1B1 in kinetics is confirmed, as is the possible association of CYP3A5 with efficacy and safety and of APOC1 with efficacy. There are also positive results for other genes that should be studied further to confirm their association with rosuvastatin.