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Objective: Metabolic-associated fatty liver disease (MAFLD) is new nomenclature for the fatty liver condition associated with metabolic dysfunction. This study aimed to investigate the association between apolipoprotein B/A1 (apo B/A1) ratio, lipoprotein(a), and MAFLD in a Korean population., Methods: This study consisted of 14,419 subjects in the Korean population. Multivariate logistic regression was conducted to analyze the association between apo B/A1 ratio and MAFLD., Results: The prevalence of MAFLD in the general Korean population was 34.5%. The apo B/A1 ratio (odds ratio: 3.913, P = .019) was independently associated with MAFLD. Lipoprotein(a) was significantly lower in patients with MAFLD with hepatic fibrosis (P < .0001)., Conclusion: Apolipoprotein B/A1 ratio and lipoprotein(a) have opposite associations with MAFLD. This study suggests that lipoprotein(a) should be used with caution as a biomarker for MAFLD, especially in patients with hepatic fibrosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Genomic studies have illuminated the alterations in pathways underlying T-cell acute lymphoblastic leukemia (T-ALL) pathogenesis, but detailed mutation data by next-generation sequencing have not been reported in Korean patients. We aimed to investigate mutation frequency, spectrum, and pattern in the Korean patients with T-ALL. We designed a multigene panel targeting 101 genes and validated it using 10 reference materials. The mutation analysis was done in a total of 10 patients with T-ALL. Clinical data and laboratory tests including immunophenotyping, cytogenetics, and molecular genetic tests were also investigated. All of the 10 patients harbored at least one mutation (range 1-6 per patient). A total of 34 clinically significant mutations including 15 novel mutations were identified in 23 genes. The median of variant allelic frequencies (VAFs) and blasts were counted upto 33% (range 5-91%) and 79% (range 38-90%), respectively. Recurrent mutations were involved in epigenetic regulators (60%), NOTCH1 signaling (40%), PI3K-AKT (40%), JAK-STAT (30%), and transcription factors (30%). We found that both NOTCH signaling and JAK-STAT signaling were positively associated with epigenetic regulators, while showed mutually exclusive patterns with PI3K-AKT pathway. This study showed that the frequency of mutations in epigenetic regulators in Korean patients was significantly higher than expected. Distribution of VAF as well as mutation spectrum is considerably heterogeneous in Korean patients with T-ALL. Although from a limited number of patients, this study provides the first detailed mutational portrait of T-ALL of Korean patients, and gives additional insight into molecular pathogenesis of the disease.

Six undescribed phenolic derivatives along with thirty two known compounds were isolated from the twigs of Betula schmidtii. The chemical structures were characterized through extensive spectroscopic analysis and chemical methods. All known compounds were first isolated in this plant. The anti-inflammatory effect of the isolates was tested by measuring nitric oxide production in lipopolysaccharide-activated BV-2 cells. Isotachioside, 4-allyl-2-hydrophenyl 1-O-β-D-apiosyl-(1 → 6)-β-D-glucopyranoside, genistein 5-O-β-D-glucoside, and prunetinoside showed a slight potency to lower the NO production against LPS-activated microglia with IC 50 values of 23.9, 25.3, 28.8, and 34.0 μM, respectively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Krebs von den Lungen 6 (KL-6) is a sensitive marker for diagnosing, monitoring, and predicting the prognoses of interstitial lung diseases (ILDs). This study aimed to evaluate the performance of the Nanopia KL-6 assay (Sekisui Medical, Tokyo, Japan) and to test the relationship between KL-6 concentrations and clinical results., Methods: In total, 230 patients diagnosed as having ILDs were enrolled. All underwent high-resolution computed tomography (HRCT) followed by the pulmonary function test (PFT). We also enrolled 116 disease controls and 200 healthy controls. Evaluation of the Nanopia KL-6 assay involved determination of precision, linearity, and limit of quantification (LOQ). Results from the Nanopia KL-6 assay were compared with those from ELISA and correlated with the HRCT and PFT results., Results: The within-laboratory precisions were <2% of CV, and linearity was acceptable between 52.2 and 4,966.5 U/mL. The LOQ was 45.2 U/mL. Nanopia and ELISA results were strongly correlated ( r =0.979). The average concentration of KL-6 was greater in ILD patients (711.5 U/mL) than in the disease (168.4 U/mL) and healthy (209.4 U/mL) controls. Serum KL-6 concentrations were strongly and moderately correlated with the extent of lung involvement and presence of typical HRCT abnormalities, respectively, and moderately correlated with PFT parameters., Conclusions: The overall analytical and clinical performance of the Nanopia KL-6 assay was acceptable. Our study is the first to compare assay platforms and show correlations between KL-6 concentrations and HRCT or PFT results in Korean ILD patients., Competing Interests: The authors declare that there are no conflicts of interest., (© The Korean Society for Laboratory Medicine.)

Background: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS., Methods: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature., Results: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1)., Conclusions: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients.

Background: The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC., Methods: A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients., Results: The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr)., Conclusions: AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominant hereditary disease characterized by corneal lattice dystrophy, peripheral neuropathy, and cutis laxa. So far, no Korean patients with HGA have been reported. A 58-yr-old man presented with involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy. His mother, maternal uncle, two sisters, and son suffered from the same symptoms. Electrophysiological studies revealed signs of chronic denervation in the cervical and lumbar regions, mild sympathetic autonomic dysfunction, and bilateral facial nerve dysfunction. Diagnostic whole-exome sequencing (WES) revealed a p.D214Y heterozygous mutation in the gelsolin gene in affected members. We present the first report of a Korean family with HGA diagnosed by WES. WES facilitated a clinical diagnosis of HGA in patients with undiagnosed neuropathies.

Background: Most cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH., Methods: A total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced., Results: The mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH., Conclusions: The mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.

Autosomal dominant non-syndromic hearing loss (AD-NSHL) is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES) and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP) chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A) in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15) described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3(rd) alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL.

Background: The purpose of the present study was to conduct a comprehensive evaluation of clinical and metabolic factors in order to determine the characteristics of urolithiasis in a Korean population, compared with other ethnic groups. In addition, clinical and metabolic factors associated with calcium oxalate (CaOx) and uric acid (UA) stone formation were compared., Methods: A total of 211 Korean patients with urolithiasis were analysed. Biochemical components in 24-hour urine were determined and the relative supersaturation (RSS) was calculated using the EQUIL 3 software program. Physical analysis of stone composition using Fourier Transform-Infrared spectrometry (FT-IR), blood chemistry, and demographics were also investigated., Results: A previous history of urolithiasis and male gender were found to be clinical risk factors related to urolithiasis. Metabolic abnormalities, including hypercalciuria, low urine volume, natriuresis, hypocitraturia, and hyperoxalaturia were commonly found in 24-hour urine. Korean patients had higher calcium, lower citrate, lower phosphate, lower urine volume, and higher RSS with respect to UA than Caucasian patients. Patients with CaOx stone formation (n = 100) were younger and excreted a higher level of calcium and higher UA at a higher pH than patients with UA stones (n = 37). A significant difference in RSS was observed with respect to CaOx, while there was no significant difference in RSS with respect to UA between them., Conclusions: Metabolic abnormalities, including hypercalciuria, low urine volume, natriuresis, hypocitraturia, and hyperoxalaturia were important findings in Korean patients with urolithiasis. In addition, clinical and metabolic characteristics of CaOx stone formers differed in comparison with UA stone formers.

Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS., Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed., Results: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value < 0.0001)., Conclusions: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

X-linked liver glycogenosis (XLG) is caused by a mutation in the PHKA2 gene which encodes the alpha subunit of phosphorylase kinase (PHK). Although XLG is not a rare disease, there have been no reports of PHKA2 mutations in Koreans. A 5-year-old boy presented with easy fatigability and hepatomegaly. Liver enzymes were increased and liver histology revealed deposition of glycogen. The PHK activity was markedly decreased compared to control. No amplification was observed at exon 8 of the PHKA2 gene, as a result of the deletion of exon 8. Sequence analysis revealed a hemizygous deletion in the region of exon 8 (c.717+781&#95;864+225del1626). The patient was diagnosed as having XLG I. To the best of our knowledge, this is the first report of XLG I in Koreans.