Comparison and Validation of 10 Equations Including a Novel Method for Estimation of LDL-cholesterol in a 168,212 Asian Population

Rim, John Hoon,Lee, Yong-ho,Lee, Myung Ha,Kim, Ha Yan,Choi, Jiin,Lee, Byung-Wan,Kang, Eun Seok,Lee, Hyun Chul,Kim, Jeong-Ho,Lee, Sang-Guk,Cha, Bong-Soo,Azmoudeh-Ardalan., Farid Williams & Wilkins Co 2016 Medicine Vol.95 No.14

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Low-density lipoprotein cholesterol (LDL-C) is frequently estimated using the empirical Friedewald equation. We compared the accuracy of the novel equation named as the 180-cell method (180-c), which estimates LDL-C using a stratification approach, to those of 9 previously suggested formulas, including the Friedewald equation.</P><P>We compared the accuracy of 10 equations by calculating intraclass correlation coefficient (ICC) and weighted kappa index in relation to direct LDL-C measurement values. Two independent populations used in the validation were the Severance Hospital LDL-C (SHL) registry (n = 164,358) and the Korea National Health and Nutrition Examination Survey (KNHANES) 2009 to 2010 (n = 3,854), each representing the hospital patient population and the general Korean population, respectively.</P><P>The 180-c and DeLong equations showed the highest ICCs, indicating the best agreement with direct LDL-C measurement. The 180-c and Chen equations showed the highest kappa indices. For the hypertriglyceridemic subpopulation from SHL, the 180-c equation showed the best agreement with direct LDL-C measurement in terms of ICC.</P><P>We compared the novel 180-c method for LDL-C estimation with 9 previous formulas in a non-US population as the first external validation. The 180-c equation, with Chen equation, appeared to be more accurate than the Friedewald equation. Although the DeLong equation showed better performance in the hypertriglyceridemic subpopulation, the 180-c equation performed appropriately in Asian population.</P></▼2>

Isodicentric Chromosome 15 Syndrome in a Korean Patient With Café-au-lait Spots

John Hoon Rim,Hee Jung Chung,Saeam Shin,Seo-Jin Park,최종락 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.4

Clinical Utility of Bone Marrow Study in Gaucher Disease: A Case Report of Gaucher Disease Type 3 With Intractable Myoclonic Seizures

John Hoon Rim,백민열,윤선옥,허경,송재우 대한진단검사의학회 2016 Annals of Laboratory Medicine Vol.36 No.2

Clinical and Molecular Delineation of a Novel De Novo 4q28.3–31.21 Interstitial Deletion in a Patient with Developmental Delay

John Hoon Rim,유종하,김성우,한성희 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.6

Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population

Jun, Ikhyun,Rim, John Hoon,Kim, Mee Kum,Yoon, Kyung-Chul,Joo, Choun-Ki,Kinoshita, Shigeru,Seo, Kyoung Yul,Ueta, Mayumi British Medical Association 2019 British journal of ophthalmology Vol.103 No.4

<P><B>Background/aims</B></P><P>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of diseases that cause an acute vesiculobullous reaction in the skin and mucous membranes. The occurrence of these diseases is associated with various drugs, a large proportion of which is comprised cold medicines (CM). We try to investigate the association between human leucocyte antigen (HLA) class I genes and CM-related SJS/TEN (CM-SJS/TEN) with severe ocular complications (SOC) in the Korean population.</P><P><B>Methods</B></P><P>This multicentre case-control study enrolled 40 Korean patients with CM-SJS/TEN with SOC and 120 age-matched and sex-matched Korean healthy volunteers between January 2012 and May 2014. HLA genotyping was performed using PCR followed by hybridisation with sequence-specific oligonucleotide probes.</P><P><B>Results </B></P><P>The carrier frequency and gene frequency of HLA-A*02:06 were 37.5 % and 20.0 %, respectively, in patients, and 16.7 % and 9.6 %, respectively, in controls (p=0.018). The carrier frequency of HLA-C*03:04 was 30 % in patients and 10.8 % in controls, and gene frequency of HLA-C*03:04 was 15 % in patients and 5.4 % in controls (p=0.003). The carrier frequency and gene frequency of HLA-C*03:03 were 2.5 % and 1.3 %, respectively, in patients, and 20 % and 10.4 %, respectively, in controls (p=0.006).</P><P><B>Conclusions </B></P><P>As per our results, we suggest that HLA-A*02:06 and HLA-C*03:04 might be positive markers for CM-SJS/TEN with SOC, and HLA-C*03:03 might be an indicator of protection against CM-SJS/TEN with SOC in the Korean population.</P>

Associations of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B With Cardiovascular Disease Occurrence in Adults: Korean Genome and Epidemiology Study

Yun Shin Young,Rim John Hoon,Kang Hyein,Lee Sang-Guk,Lim Jong-Baeck 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.3

Background: Despite the superiority of non-HDL cholesterol (non-HDL-C) and apolipoprotein B (ApoB) as lipid markers for atherosclerotic cardiovascular disease (ASCVD), these are only suitable as secondary markers. We compared LDL cholesterol (LDL-C), non-HDL-C, and ApoB concentrations with respect to the occurrence of cardiovascular disease in adults enrolled in the Korean Genome and Epidemiology Study (KoGES). Methods: We used information on age; sex; medical history; family history of ASCVD; current lipid-lowering therapy; current smoking status; and creatinine, total cholesterol, HDL-C, LDL-C, triglyceride, and ApoB concentrations from 5,872 KoGES participants without ASCVD. New ASCVD development was monitored during the 8-year follow-up period. Adjusted hazard ratios (aHRs) for ASCVD of LDL-C, non-HDL-C, and ApoB concentrations were calculated based on the multivariate Cox regression analyses. The participants were also grouped as low and high according to the median values for each lipid marker, and calculated aHRs of each group combined by two lipid makers. Results: ApoB showed the highest aHR per 1-SD for ASCVD (1.26; 95% confidence interval [CI], 1.11–1.43), followed by non-HDL-C (1.25; 95% CI, 1.11–1.41) and LDL-C (1.20; 95% CI, 1.06–1.37). The group with low LDL-C and high ApoB concentrations had a significantly higher aHR for ASCVD (1.61; 95% CI, 1.05–2.48) compared to the reference group values (low LDL-C and low ApoB concentrations). The aHR for the group with high LDL-C and low ApoB concentrations was not significant (1.30; 95% CI, 0.79–2.16). Conclusions: ApoB, non-HDL-C, and LDL-C are independent risk factors for ASCVD. Increases in the aHR per 1-SD for ASCVD were more strongly affected by ApoB, followed by non-HDL-C and LDL-C. Participants with low LDL-C and high ApoB concentrations showed increased ASCVD risk. For individuals with ASCVD risk factors, even those presenting normal LDL-C concentrations, measuring Apo

Measurement of Plasma Free Hemoglobin Using Hemolysis Index and Bilirubin Interference

Hanmil Jang,Yonggeun Cho,John Hoon Rim,Hyein Kang,이상국,임종백 대한임상검사정도관리협회 2021 Journal of Laboratory Medicine And Quality Assuran Vol.43 No.4

Plasma hemoglobin (pHb) is measured when hemolysis is suspected as a result of biochemical, immunological, and mechanical conditions. In this study, we evaluated the clinical feasibility of the hemolysis index (H-index) for pHb measurement using automated chemistry analyzers. A total of 176 plasma samples were analyzed for pHb in the Severance Hospital using a Lambda 365 UV/Vis spectrophotometer (PerkinElmer, USA) and Fairbanks method 2. The remnant samples after pHb measurement were then analyzed for total bilirubin, and H-indices were determined using the automated Atellica CH930 system (Siemens, Germany) and Cobas c702 system (Roche, USA). The equivalence and correlation among the methods were evaluated using Passing-Bablok regression analysis and Spearman’s correlation analysis. All the methods showed high correlations with each other. However, the H-indices showed a negative constant bias compared to the Fairbanks method 2. When a cut-off value of 33.2 mg/dL was applied for diagnosis of hemolysis, 13 samples were determined positive by Fairbanks method 2 but negative by H-indices. These discordant results occurred mostly among samples with total bilirubin levels higher than 3 mg/dL (12 out of 13 samples). The correlation between total bilirubin and pHb measured by Fairbanks method 2 showed the largest correlation coefficient (R =0.347) and slope. These results suggest that the pHb measured by Fairbanks method 2 is more prone to bilirubin interference. In summary, our results suggest that H-indices from both automated chemistry analyzers possess excellent clinical feasibility for pHb measurements and have minimum total bilirubin interference compared to traditional measurement via Fairbanks method 2.

Mutations of <i>ADAMTS9</i> Cause Nephronophthisis-Related Ciliopathy

Choi, Yo Jun,Halbritter, Jan,Braun, Daniela A.,Schueler, Markus,Schapiro, David,Rim, John Hoon,Nandadasa, Sumeda,Choi, Won-il,Widmeier, Eugen,Shril, Shirlee,Kö,rber, Friederike,Sethi, Sidharth K. Elsevier 2019 American journal of human genetics Vol.104 No.1

<P>Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide cohort of 800 additional families affected by NPHP-RC. We identified two <I>ADAMTS9</I> mutations (c.4575_4576del [p.Gln1525Hisfs<SUP>∗</SUP>60] and c.194C>G [p.Thr65Arg]) that appear to cause NPHP-RC. Although ADAMTS9 is known to be a secreted extracellular metalloproteinase, we found that ADAMTS9 localized near the basal bodies of primary cilia in the cytoplasm. Heterologously expressed wild-type ADAMTS9, in contrast to mutant proteins detected in individuals with NPHP-RC, localized to the vicinity of the basal body. Loss of ADAMTS9 resulted in shortened cilia and defective sonic hedgehog signaling. Knockout of <I>Adamts9</I> in IMCD3 cells, followed by spheroid induction, resulted in defective lumen formation, which was rescued by an overexpression of wild-type, but not of mutant, ADAMTS9. Knockdown of <I>adamts9</I> in zebrafish recapitulated NPHP-RC phenotypes, including renal cysts and hydrocephalus. These findings suggest that the identified mutations in <I>ADAMTS9</I> cause NPHP-RC and that ADAMTS9 is required for the formation and function of primary cilia.</P>

Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment

Jinsei Jung,Haiyue Lin,Young Ik Koh,Kunhi Ryu,Joon Suk Lee,John Hoon Rim,Hye Ji Choi,Hak Joon Lee,Hye-Youn Kim,Seyoung Yu,Hyunsoo Jin,Ji Hyun Lee,Min Goo Lee,Wan Namkung,Jae Young Choi,Heon Yung Gee 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

KCNQ4 is frequently mutated in autosomal dominant non-syndromic hearing loss (NSHL), a typically late-onset, initially high-frequency loss that progresses over time (DFNA2). Most KCNQ4 mutations linked to hearing loss are clustered around the pore region of the protein and lead to loss of KCNQ4-mediated potassium currents. To understand the contribution of KCNQ4 variants to NSHL, we surveyed public databases and found 17 loss-of-function and six missense KCNQ4 variants affecting amino acids around the pore region. The missense variants have not been reported as pathogenic and are present at a low frequency (minor allele frequency < 0.0005) in the population. We examined the functional impact of these variants, which, interestingly, induced a reduction in potassium channel activity without altering expression or trafficking of the channel protein, being functionally similar to DFNA2-associated KCNQ4 mutations. Therefore, these variants may be risk factors for late-onset hearing loss, and individuals harboring any one of these variants may develop hearing loss during adulthood. Reduced channel activity could be rescued by KCNQ activators, suggesting the possibility of medical intervention. These findings indicate that KCNQ4 variants may contribute more to late-onset NSHL than expected, and therefore, genetic screening for this gene is important for the prevention and treatment of NSHL.

Performance Evaluation of the DxC 700 AU Chemistry Analyzer in Hemoglobin A1c Measurement

Choi Yu Jeong,Kang Hyein,Cho Chan-Ik,Rim John Hoon,Lee Sang-Guk,Lim Jong-Baeck 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.2

Background: Accurate measurement of glycated hemoglobin (HbA1c) is crucial for a diabetes diagnosis and subsequent patient management. The detection method and presence of variant Hb can interfere with HbA1c measurements. We evaluated the HbA1c-measuring performance of the DxC 700 AU (Beckman Coulter, Brea, CA, USA) immunoassay-based device in comparison with another immunoassay device and the reference method. Methods: A total of 120 normal and 14 variant Hb samples were analyzed using the Cobas c 513 (Roche Diagnostics, Mannheim, Germany) and DxC 700 AU analyzers. Variant Hb samples were also analyzed using the reference method, along with 20 normal samples. The accuracy, precision, linearity, and carryover were determined. Results: DxC 700 AU results strongly correlated with those of Cobas c 513 and exhibited accuracy in comparison with the reference method. The within-run, between-run, between-day, and total imprecision (%CV) values for the low- and high-concentration control materials were below 2%. The results of DxC 700 AU were linear over a wide HbA1c range (3.39%–18.30%). Although DxC 700 AU performed well in the presence of variant Hb, the HbA1c concentration was underestimated in the presence of fetal Hb. The possibility of interference from a high HbH proportion could not be ruled out. Conclusions: The overall analytical performance of DxC 700 AU was acceptable. The device is accurate, precise, and linear over a wide HbA1c concentration range. Although DxC 700 AU results highly correlated with those of Cobas c 513, caution should be exercised in cases of high HbF and HbH concentrations.