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The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype–phenotype correlation not only in male patients but also in female patients with XLAS. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD. Methods: The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive–compulsive disorder (OCD). Results: The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke's R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke's R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke's R2 = 4.91%, OR = 1.53, p = 0.043). Conclusion: The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders. [ABSTRACT FROM AUTHOR]

Th2-dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 and IL-13 are typical pleiotropic Th2 cytokines that play a central role in IgE-dependent inflammatory reactions. Single-nucleotide polymorphisms (SNPs) in IL-4 and IL-13 have been reported in patients with allergic disease from numerous countries. Gene-gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL-4, IL-13, IL-4R, IL-13Rα1 and IL-13Rα2 genes for 1089 case-control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in these genes. We also searched for gene-gene interactions among these five genes. Our data identified an association between rs3091307 and rs20541 in the IL-13 gene and between rs2265753 and rs2254672 in the IL-13Rα1 gene and the AD phenotype. In particular, three of the four SNPs were especially predictive of the allergic type of AD (ADe), and the haplotype TCGG in the IL-13Rα1 gene showed significant association with AD, especially ADe. Furthermore, the combination of rs3091307 GG/ rs2265753 GG (IL-13/IL-13Rα1) conveyed a significantly higher risk for developing ADe. However, we did not identify any SNPs in the IL-4, IL-4R and IL-13Rα2 genes that were associated with AD. As IL-13Rα1 is most likely expressed in Th17 cells rather than in Th2 cells, these data suggest diversity in the classification of Th cells that needs to be verified in future studies. [ABSTRACT FROM AUTHOR]

This multi-center cohort study included 3401 myopic laser in situ keratomileusis (LASIK) procedures conducted in 1756 myopia patients between 2002 and 2005. Pre- and postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and manifest refraction spherical equivalent (SE) were recorded. Factors predicting low postoperative efficacy (defined as a postoperative UCVA < 0.5) were identified using univariate and multivariate logistic regression analysis. Compared with 1 month postoperatively, logMAR UCVA at 3 months postoperatively was significantly decreased (p = 0.002) and that at 2 and 3 years was significantly increased (p < 0.001). LogMAR BCVA at 2 years postoperatively was significantly decreased compared with 1 month postoperatively (p = 0.008). Over the 3-year postoperative period, overall refractive predictability within ±1.00 D and ±0.50 D ranged from 69.0% to 86.2% and from 43.3% to 67.8%, respectively. This also decreased from 1 month to 6 months postoperatively (p < 0.005). Multivariate logistic regression analysis using generalized estimating equations, revealed that higher preoperative SE (odds ratio [OR], 2.58 and 7.23; p < 0.001) and lower preoperative BCVA (OR, 2.44; p = 0.003) were predictive of a low postoperative efficacy. In summary, myopic LASIK can be effective and safe with a high refractive predictability in a Korean population, but myopic regression occurs over time. Higher preoperative SE and lower preoperative BCVA are predictive of a low postoperative efficacy. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the genetic structure of Streptococcus pneumoniae isolated from Korean children prior to the use of heptavalent pneumococcal conjugate vaccine (PCV7). A total of 278 pneumococcal isolates were obtained from invasive (n = 77) and noninvasive (n = 201) specimens from children <5 years of age that visited the Seoul National University Children''s Hospital between 1995 and 2005; these samples were serotyped. Two hundred seventy-eight isolates were characterized by multilocus sequence typing, antibiotic susceptibility pattern testing with the E-test. The common serotypes were 19F (22.7%), 23F (19.1%), 19A (14.4%), 6B (11.2%), 6A (8.3%), 14 (5.4%), and 9V (4.3%); these 7 serotypes accounted for 85.3% of the 278 isolates. The isolates belonged to 23 serotypes and 81 sequence types (STs) (including 48 newly discovered STs). The eBURST analysis showed 7 clonal complexes (CCs). CC271 was the main CC of serogroup 19; CC81 and CC3115, serotype 6A; CC81 and CC880, serotype 23F; CC90, serotype 6B; CC166, serotype 9V; and CC554, serotype 14. Nonsusceptibility rates to penicillin and erythromycin among the invasive isolates were 9.1% and 94.8%, respectively. The resultant database may be useful for postvaccine surveillance. [Copyright &y& Elsevier]

Abstract: Background: The histology of atopic dermatitis includes dilated, tortuous vessels within the papillary dermis and perivascular edema. Method: This study included 1120 case-control samples (646 AD patients and 474 normal controls), for which we genotyped 34 SNPs from four VEGF family genes and the FLT4 gene. For the rs11607007 SNP in the VEGFB gene and three SNPs (rs10085109, rs3736062, and rs11949194) in the FLT4 gene, which had significant p-values in the initial stage, were further investigated using 1132 independent samples (440 AD patients and 692 normal controls). Result: Of the four SNPs, rs10085109 in the FLT4 gene was only significantly associated with the AD phenotype in both initial and replication samples. Although no SNPs in the VEGFA gene were significantly associated with AD, the rs2010963 SNP had a marginally significant effect on log-eosinophil counts. Conclusion: The rs10085109 SNP in the FLT4 gene were associated with susceptibility to AD. [Copyright &y& Elsevier]

Abstract: Background: The acute skin lesions of atopic dermatitis (AD) are associated with Th2 cells; however, the chronic skin lesions of AD are associated with Th1 cells via the action of IL-12. Objective: We evaluated the associations of single nucleotide polymorphisms (SNPs) and haplotype in the IL-12 and IL-12 receptor genes, and determined the gene–gene interactions between the SNPs of these genes and the SNPs of the IL-18 gene that we previously reported. Method: We genotyped 24 SNPs from 4 IL-12/IL-12R genes for 1089 case–control samples (631 AD patients and 458 normal controls). We measured the serum IL-12 concentrations in 89 individuals (79 AD patients and 10 controls) by ELISA. We analyzed the SNPs and haplotypes in each gene and also searched for the gene–gene interactions. Result: The rs582504 (IVS−798A/T) SNP and the haplotype TA (rs582054 and rs2243151) in the IL-12A gene, and the rs438421 (IVS12+1266T/C) SNP and the haplotype CCA (rs375947, rs438421, and rs1870063) in the IL-12RB1 gene were significantly associated with the AD phenotype. We showed that the rs438421 polymorphism in the IL-12RB1 (TT) gene and the rs2066446 polymorphism in the IL-12RB2 (AA) gene had a significant interaction to develop the ADe phenotype (allergic type of AD), and those individuals with the risk alleles, TT/AA/CC (IL-12RB1/IL-12RB2/IL-18), have more than a 10-fold increased risk to develop ADe. Conclusion: This study provides evidence for a significant interaction between the IL-12RB1 and IL-12RB2 genes that contribute to a 4-fold increased risk for developing ADe. In addition to the IL-12R interaction, we suggest that the IL-18 gene can significantly interact with the IL-12R gene to develop ADe. In addition to the interaction, the SNPs and haplotypes in the IL-12A and IL-12RB1 genes are independently and significantly associated with the AD phenotype, and especially with the ADe phenotype. This data may contribute to our understanding of AD genetic interactions and account for the additional risk of certain patients to develop AD. [Copyright &y& Elsevier]