Targeted next-generation sequencing for comprehensive genetic analysis of external apical root resorption during orthodontic treatment with premolar extraction in the Korean population.

INTRODUCTION: External apical root resorption (EARR) is one of the most common unfavorable consequences of orthodontic treatment and causes loss of tooth structure. The present study aimed to investigate the genetics of EARR using next-generation sequencing comprehensively. METHODS: Targeted next-generation sequencing was performed for comprehensive genetic analysis of 118 Korean orthodontic patients. The patients were divided into 2 groups on the basis of their EARR value. The association of clinical and genetic parameters with EARR was assessed using the χ2 test or t test for matched pairs, followed by Bonferroni correction and linear regression analysis. In addition, haplotype analysis and in silico prediction were conducted to evaluate functional effects. RESULTS: No statistically significant difference was observed between clinical and treatment-related parameters and EARR. The single nucleotide polymorphisms SPP1 rs9138 (P = 0.001) and SFRP2 rs3810765 (P = 0.04) showed only nominal significance between EARR groups. However, these 2 SNPs were not significant after Bonferroni correction for multiple testing (cutoff P = 0.05/142 = 3.52 × 10-4). Variations in SPP1 rs9138 and SFRP2 rs3810765 may be related to EARR during orthodontic treatment. In summary, not only genes related to inflammatory reactions but also those related to Wnt signaling to affect the degree of EARR during orthodontic teeth movement.

Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery.

PURPOSE: Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascular risk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify and replicate the genetic variants associated with ACEI-related AEs in the Korean population. MATERIALS AND METHODS: A two-stage approach employing genome-wide association study (GWAS)-based discovery and replication through target sequencing was used. In total, 1300 individuals received ACEIs from 2001 to 2007; among these, 228 were selected for GWAS. An additional 336 patients were selected for replication after screening 1186 subjects treated from 2008 to 2018. Candidate genes for target sequencing were selected based on the present GWAS, previous GWASs, and data from the PharmGKB database. Furthermore, association analyses were performed between no AE and AE or cough groups after target sequencing. RESULTS: Five genes, namely CRIM1, NELL1, CACNA1D, VOPP1, and MYBPC1, were identified near variants associated with ACEI-related AEs. During target sequencing of 34 candidate genes, six single-nucleotide polymorphisms (SNPs; rs5224, rs8176786, rs10766756, rs561868018, rs4974539, and rs10946364) were replicated for association with all ACEI-related AEs. Four of these SNPs and rs147912715 exhibited associations with ACEI-related cough, whereas four SNPs (rs5224, rs81767786, rs10766756, and rs4974539 near BDKRB2, NELL1, NELL1 intron, and CPN2, respectively) were significantly associated with both categories of AEs. CONCLUSION: Several variants, including novel and known variants, were successfully replicated and found to have associations with ACEI-related AEs. These results provide rare and clinically relevant information for safer use of ACEIs.

GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study.

Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.