Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study

Introduction: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.Methods: All 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4_89, padi4_90, and padi4_92) and one synonymous (padi4_104) singlenucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI).Results: A functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms.Conclusions: A haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contri bution is affected by gene-gene interactions with HLADRB1 SE alleles.We are grateful to many research workers for assistance with sample preparation, data collection, and technical study. Dr. Bang's work was supported by a grant from the Korea Healthcare Technology R&D Project (A090706). Dr. Bae's work was supported by a grant from the Korea Healthcare Technology R&D Project (A084794 and A010252). Dr. Kang's work was supported by a grant from the Research Program for New Drug Target Discovery (M10748000231-08N4800-23110)

Phenylalanine ammonia-lyase expression and pyranocoumarin accumulation in Angelica gigas plantlets exposed to light-emitting diodes

Angelica gigas (Dang Gui) is an important medicinal plant. In this study, we examined the accumulation of pyranocoumarin (decursin and decursinol angelate) and the expression of phenylalanine ammonia-lyase (PAL) in Korean angelica plantlet grown under different light-emitting diodes (LEDs) (red, orange, green, blue, and white). Three weeks after LED exposure (WAE), the transcript levels of phenylalanine ammonia-lyase mRNA in seedlings grown under orange LEDs were 4-, 18-, and 7-fold higher than those in seedlings grown under green, blue, and white LEDs, respectively. The decursinol angelate content was almost double than the decursin content. The highest levels of decursin (3.2 mg/g dry weight) and decursinol angelate (6 mg/g dry weight) were detected in plants grown under orange LEDs, at 2 WAE. Therefore, we suggest that orange LEDs may affect decursin and decursinol angelate accumulation. The findings of this study could help to determine an effective strategy for producing secondary metabolites in A. gigas using LED technology

Population Dynamics of Five Anopheles Species of the Hyrcanus Group in Northern Gyeonggi-do, Korea

To investigate the population densities of potential malaria vectors, Anopheles species were collected by light traps in malaria endemic areas, Paju and Gimpo, Gyeonggi-do of Korea. Five Anopheles Hyrcanus sibling species (An. sinensis, An. pullus, An. lesteri, An. kleini, and An. belenrae) were identified by PCR. The predominant species, An. pullus was collected during the late spring and mid-summer, while higher population consists of An. sinensis were collected from late summer to early autumn. These 2 species accounted for 92.1% of all Anopheles mosquitoes collected, while the other 3 species accounted for 7.9%. Taking into account of these population densities, late seasonal prevalence, and long-term incubation period (9-13 months) of the Korean Plasmodium vivax strain, An. sinensis s.s is thought to play an important role in the transmission of vivax malaria in the study areas

The Relationship between Lewis/Secretor Genotypes and Serum Carbohydrate Antigen 19-9 Levels in a Korean Population

Background : The Lewis histo-blood group system consists of 2 major antigens-Le(a) and Le(b)-and a sialyl Lewis antigen-carbohyd rate antigen (CA) 19-9. We investigated the distribution of Lewis genotypes and evaluated the relationship between the Lewis/Secretor genotypes and the serum level of CA 19-9 in a Korean population to identify whether the serum CA 19-9 levels are influenced by the Lewis/Secretor genotypes. Methods : The study included 242 individuals who had no malignancies. Lewis genotyping was performed for the 59T>G, 508G>A and 1067T>A polymorphic sites. The Secretor genotype was determined through analysis of the 357C>T and 385A>T polymorphic sites and the fusion gene. Serum CA 19-9 level was analyzed using an electrochemiluminescence immunoassay. Results : Individuals carrying the 3 common genotypes-Le/Le, Le/le(59,508), and Le/le(59,1067)-accounted for 95% of the study population. In the Korean population, the allelic frequencies of Le, Le(59)le(59,508) and le(59,1067) were 0.731, 0.010, 0.223, and 0.035, respectiveiy. We found a significant difference in serum CA 19-9 concentrations among the 9 LewislSecretor genotype groups (P<0.001). The serum CA 19-9 levels in subjects with genotype groups 1 and 2 (Le/- and se/se) were higher than those with genotype groups 3-6 (Le/- and Se/-; 15.63 vs 6.64 kU/L, P<0.001). Conclusions : Le/Le(59,508), and Le/le(59,1067) are frequent Lewis genotypes in Koreans. Because serum CA 19-9 levels are significantly influenced by the LewislSecretor genotypes, caution is suggested when interpreting the serum CA 19-9 levels. (Korean J Lab Med 2010;30:51-7)SONG SY, 2008, KOREAN J HEMATOL, V43, P34Park KU, 2005, ANN HEMATOL, V84, P656, DOI 10.1007/s00277-005-1041-5Hayashi N, 2004, PATHOBIOLOGY, V71, P26, DOI 10.1159/000072959Hamajima N, 2002, J MOL DIAGN, V4, P103HAMAJIMA N, 2002, GASTRIC CANCER, V5, P194Liu TC, 2000, ANN HEMATOL, V79, P599Lamerz R, 1999, ANN ONCOL, V10, P145Vestergaard EM, 1999, CLIN CHEM, V45, P54Liu YH, 1999, J HUM GENET, V44, P181Kim MJ, 2002, YONSEI MED J, V43, P427SHIBATA A, 2003, GASTRIC CANCER, V6, P8Liu YH, 1999, J FORENSIC SCI, V44, P82Liu YH, 1998, HUM GENET, V103, P204Pang H, 1998, HUM GENET, V102, P675Narimatsu H, 1998, CANCER RES, V58, P512Liu YH, 1996, J FORENSIC SCI, V41, P1018Koda Y, 1996, AM J HUM GENET, V59, P343Kudo T, 1996, J BIOL CHEM, V271, P9830ROUQUIER S, 1995, J BIOL CHEM, V270, P4632KELLY RJ, 1995, J BIOL CHEM, V270, P4640NISHIHARA S, 1994, J BIOL CHEM, V269, P29271MOLLICONE R, 1994, J BIOL CHEM, V269, P20987

Genetic evidence of illegal trade in protected whales links Japan with the US and South Korea

We report on genetic identification of ‘whale meat’ purchased in sushi restaurants in Los Angeles, CA (USA) in October 2009 and in Seoul, South Korea in June and September 2009. Phylogenetic analyses of mtDNA cytochrome b sequences confirmed that the products included three species of whale currently killed in the controversial scientific whaling programme of Japan, but which are protected from international trade: the fin, sei and Antarctic minke. The DNA profile of the fin whale sold in Seoul established a match to products purchased previously in Japan in September 2007, confirming unauthorized trade between these two countries. Following species identification, these products were handed over to the appropriate national or local authorities for further investigation. The illegal trade of products from protected species of whales, presumably taken under a national permit for scientific research, is a timely reminder of the need for independent, transparent and robust monitoring of any future whaling

DEL 적혈구에 의한 항-D 동종면역

Extremely weak D variants called DEL are serologically detectable only by adsorption-elution techniques. A nucleotide change of exon 9 in RHD gene, RHD (K409K, 1227G>A) allelic variant is present in almost all the DEL individuals of East Asians. No DEL phenotype has yet been shown to induce a primary alloanti-D immunization in East Asia. A 68-yr-old D-negative Korean man was negative for anti-D at admission, and he developed alloanti-D after transfusion of red blood cells (RBC) from 4 apparently D-negative donors. Four donors who typed D-negative by routine serologic test were analyzed by real-time PCR for RHD gene and RHD (K409K). One donor was found to have RHD (K409K), This is the first case in which DEL RBCs with RHD (K409K) induced a primary alloanti-D immunization in Asian population. Because the DEL phenotype can induce an anti-D immunization in D-negative recipients, further discussion is needed whether RhD negative donors should be screened by molecular method and what an efficient genotyping method is for detecting the RHD gene carriers in Korea. (Korean J Lab Med 2009;29:361-5)Polin H, 2009, TRANSFUSION, V49, P676, DOI 10.1111/j.1537-2995.2008.02046.xFlegel WA, 2009, TRANSFUSION, V49, P465, DOI 10.1111/j.1537-2995.2008.01975.xSun CF, 2008, ANN CLIN LAB SCI, V38, P258Richard M, 2007, TRANSFUSION, V47, P852, DOI 10.1111/j.1537-2995.2007.01199.xLuettringhaus TA, 2006, TRANSFUSION, V46, P2128, DOI 10.1111/j.1537-2995.2006.01042.xYasuda H, 2005, TRANSFUSION, V45, P1581, DOI 10.1111/j.1537-2995.2005.00579.xWagner T, 2005, TRANSFUSION, V45, P520Gassner C, 2005, TRANSFUSION, V45, P527Kim JY, 2005, TRANSFUSION, V45, P345WAGNER FF, 2001, BMC GENET, V2, P10Avent ND, 2000, BLOOD, V95, P375Aubin JT, 1997, BRIT J HAEMATOL, V98, P356Okuda H, 1997, J CLIN INVEST, V100, P373Avent ND, 1997, BLOOD, V89, P2568HWANG YS, 1996, KOREAN J BLOOD TRANS, V7, P233DANIELS G, 1995, HUMAN BLOOD GROUPSMAK KH, 1993, TRANSFUSION, V33, P348LINCHU M, 1988, TRANSFUSION, V28, P350

Hemolytic Disease of the Newborn Associated with Anti-Jr(a) Alloimmunization in a Twin Pregnancy: The First Case Report in Korea

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women. (Korean J Lab Med 2010;30:511-5)Arriaga F, 2009, TRANSFUSION, V49, P813, DOI 10.1111/j.1537-2995.2009.02118.xPeyrard T, 2008, TRANSFUSION, V48, P1906, DOI 10.1111/j.1537-2995.2008.01787.xROBACK JD, 2008, TECHNICAL MANUAL, P411CHUNG HJ, 2007, KOREAN J BLOOD TRANS, V18, P111Ishihara Y, 2006, FETAL DIAGN THER, V21, P269, DOI 10.1159/000091354Daniels GL, 2004, VOX SANG, V87, P304Kwon MY, 2004, TRANSFUSION, V44, P197Bellver-Pradas J, 2001, AM J OBSTET GYNECOL, V184, P75STROUP M, 1970, P 23 ANN M AM ASS BL, P86KIM DW, 1995, ELS APPL ELECT MAT, V6, P185MIYAZAKI T, 1994, VOX SANG, V66, P51OGASAWARA K, 1990, ACTA HAEMATOL JAPON, V53, P1131GARRATTY G, 1990, TRANSFUS MED REV, V4, P297NANCE SJ, 1987, TRANSFUSION, V27, P449BACON J, 1986, TRANSFUSION, V26, P543LEVENE C, 1986, TRANSFUSION, V26, P119TAKABAYASHI T, 1985, TOHOKU J EXP MED, V145, P97TOY P, 1981, VOX SANG, V41, P40ORRICK LR, 1980, AM J OBSTET GYNECOL, V137, P135NAKAJIMA H, 1978, VOX SANG, V35, P265VEDO M, 1978, TRANSFUSION, V18, P569TRITCHLER JE, 1977, TRANSFUSION, V17, P177KENDALL AG, 1976, TRANSFUSION, V16, P646

Real-Time PCR Method for HPV DNA Detection

Human papillomavirus (HPV) infection is an important etiologic factor in cervical carcinogenesis. Various HPV DNA detection methods have been evaluated for clinicopathological level. For the specimens with normal cytological finding, discrepancies among the detection methods were frequently found and adequate interpretation can be difficult. 6,322 clinical specimens were submitted and evaluated for real-time PCR and Hybrid Capture 2 (HC2). 573 positive or &quot;Not Detected but Amplified&quot; (NDBA) specimens by real-time PCR were additionally tested using genetic analyzer. For the reliability of real-time PCR, 325 retests were performed. Optimal cut-off cycle threshold ( ) value was evaluated also. 78.7% of submitted specimens showed normal or nonspecific cytological finding. The distributions of HPV types by real-time PCR were not different between positive and NDBA cases. For positive cases by fragment analysis, concordance rates with real-time PCR and HC2 were 94.2% and 84.2%. In NDBA cases, fragment analysis and real-time PCR showed identical results in 77.0% and HC2 revealed 27.6% of concordance with fragment analysis. Optimal cut-off value was different for HPV types. NDBA results in real-time PCR should be regarded as equivocal, not negative. The adjustment of cut-off value for HPV types will be helpful for the appropriate result interpretation

Performance Evaluation of the GlucoDr Plus Glucometer

Background: Because strict glucose control is important for reducing the complications of diabetes, the self-monitoring of blood glucose is one of the fundamental treatment modalities. Many glucometers have been developed. In the present study, we evaluated a new glucometer: GlucoDr (TM) Plus (Allmedicus, Anyang, Gyeonggi-do, Republic of Korea). Methods: The evaluation was performed based on Clinical and Laboratory Standards Institute guidelines. Interferences by ascorbic acid, uric acid, maltose, and acetaminophen were examined, and the performance of the unit was compared to those of six other glucometers. The effects of hematocrit, of oxygen partial pressure (PaO(2)), and of multiple users were also evaluated. Results: Within-run, between-run, between- day, and total imprecision (coefficients of variation) were 0.99-4.98%. Satisfactory linearity was found for glucose concentrations of 32.5-786.5 mg/dL (R(2) = 0.9985). A comparison with the reference laboratory method showed close concordance over the entire range of concentrations evaluated (R(2) = 0.9869). No significant effects were noted due to added interferents, hematocrit, and PaO(2). Conclusions: The GlucoDr Plus showed acceptable performance in terms of precision and linearity. It was minimally affected by various interferents. GlucoDr Plus is suitable for the self-monitoring of blood glucose by patients with diabetes.Schleis TG, 2007, PHARMACOTHERAPY, V27, P1313Tsujimura S, 2006, BIOSCI BIOTECH BIOCH, V70, P654D`Orazio P, 2006, CLIN CHEM LAB MED, V44, P1486, DOI 10.1515/CCLM.2006.275Nathan DM, 2005, NEW ENGL J MED, V353, P2643Wild S, 2004, DIABETES CARE, V27, P1047*CLIN LAB STAND I, 2004, EP5A2 CLSI*CLIN LAB STAND I, 2003, EP6A CLSI*INT ORG STAND, 2003, 151972003E ISO*CLIN LAB STAND I, 2002, EP7A CLISTang ZP, 2001, CRIT CARE MED, V29, P1062Tang ZP, 2000, AM J CLIN PATHOL, V113, P75Turner RC, 1998, LANCET, V352, P837*CLIN LAB STAND I, 1995, EP9A CLSI1994, DIABETES CARE, V17, P81MERENSTEIN GB, 1993, PEDIATRICS, V92, P4741993, N ENGL J MED, V329, P977BARRETT AE, 1979, J CLIN PATHOL, V32, P893