Development of HLA-A, -B and -DR Typing Method Using Next-Generation Sequencing / 대한수혈학회지

BACKGROUND: Research on next-generation sequencing (NGS)-based HLA typing is active. To resolve the phase ambiguity and long turn-around-time of conventional high resolution HLA typing, this study developed a NGS-based high resolution HLA typing method that can handle large-scale samples within an efficient testing time. METHODS: For HLA NGS, the condition of nucleic acid extraction, library construction, PCR mechanism, and HLA typing with bioinformatics were developed. To confirm the accuracy of the NGS-based HLA typing method, the results of 192 samples HLA typed by SSOP and 28 samples typed by SBT compared to NGS-based HLA-A, -B and -DR typing. RESULTS: DNA library construction through two-step PCR, NGS sequencing with MiSeq (Illumina Inc., San Diego, USA), and the data analysis platform were established. NGS-based HLA typing results were compatible with known HLA types from 220 blood samples. CONCLUSION: The NSG-based HLA typing method could handle large volume samples with high-throughput. Therefore, it would be useful for HLA typing of bone marrow donation volunteers.

Exercise improves the effects of testosterone replacement therapy and the durability of response after cessation of treatment: A pilot randomized controlled trial / 亚洲男科学杂志(英文版)

The effects of the combination of exercise and TRT on symptoms of late-onset hypogonadism (LOH) and the durability of response after cessation of TRT were investigated. A total of fifty patients with erectile dysfunction (ED) who had a sedentary lifestyle and low serum total testosterone (T) levels were enrolled and followed for 20 weeks. Patients were randomly divided into two groups; all of them received T gel for 12 weeks and it was discontinued for 8 weeks. Patients assigned to Group II were offered a supervised exercise program for 20 weeks. Measurement of serological testing was performed and self-assessment questionnaires and Global Assessment Question (GAQ) were asked. Baseline characteristics and the initial symptom scores showed no significant difference between the two groups. Serum total T levels and the symptom scores were increased at 12 weeks in both groups, and Group II showed better results with statistical significance. There was a decrease in T levels and worsening of symptom scores at week 20 compared to week 12 in both groups, and Group II showed better results with statistical significance. On the GAQ, Group II showed higher ratio of yes at week 12 and the same tendency was sustained at week 20 with significant difference between two groups. The combination of exercise and TRT showed significant improvements in serum T levels and LOH symptoms compared to TRT alone. In addition, these improvements were maintained in the combination group with continuous exercise, even after cessation of TRT.

Anti-tumor Immune Response after Cryoablation in Renal Cell Carcinoma Murine Model

PURPOSE: Cryoablation has been used successfully for the local treatment of renal cell carcinoma. Besides local destruction, Cryoablation has an immunogenic nature. In this study, we evaluated the anti-tumor immune response induced by cryoablation in renal cell carcinoma murine model. MATERIALS AND METHODS: Renal cell carcinoma was produced in BALB/c mice by the subcutaneous inoculation of Renca cells in the thigh. After 7 days, the tumors were removed using liquid nitrogen in cryoablation group and bipolar electrocoagulation in electrocautery group. For twelve days after re-inoculation of Renca cells at contralateral thigh, tumor volumes were measured daily to assess the effect against the growth of tumor. The immunocyte levels (T4, T8, B and NK cell) were determined to evaluate immune activity by FACS (Fluorescence activated cell sorter) analysis. The effect of cryoablation to induce apoptosis of tumor was evaluated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling) assay. RESULTS: The tumor volume of cryoablation group was significantly smaller than that of electrocautery group and control (p<0.05). Comparing with control, T cell level was significantly increased after cryoablation (p<0.05), but no group had a significant difference in the levels of B cell and NK cell by FACS analysis. The apoptosis index % of cryoablation group was significantly increased than that of control group (p<0.05) by TUNEL. CONCLUSIONS: Cryoablation could result in the inhibition of re-inoculated tumor growth and induce T cell mediated immune response. The active immune response may be attributed to the apoptosis of tumor after cryoablation.

Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. MATERIALS AND METHODS: Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. RESULTS: A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. CONCLUSION: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.

Exome sequencing in a breast cancer family without BRCA mutation

PURPOSE: We performed exome sequencing in a breast cancer family without BRCA mutations. MATERIALS AND METHODS: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. RESULTS: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. CONCLUSION: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

Exome sequencing in a breast cancer family without BRCA mutation

PURPOSE: We performed exome sequencing in a breast cancer family without BRCA mutations. MATERIALS AND METHODS: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. RESULTS: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. CONCLUSION: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

Clinical Study of Non-Invasive Prenatal Testing Using Next-Generation Sequencing

BACKGROUND: Serological prenatal screening tests are widely used to detect fetal chromosomal abnormalities such as Down and Edward syndromes. After determining the presence of fetal cell-free DNA in maternal blood, the non-invasive prenatal test (NIPT) coupled with next-generation sequencing has been performed in other countries, therefore, we developed a domestic NIPT technology. METHODS: The results of genomics-based NIPT performed between April and May, 2015 were analyzed. Maternal blood samples were collected in a specific Cell-Free DNA BCT tube. The samples were then massively sequenced using MiSeq and NextSeq 500 (Illumina Inc., USA) using LabGenomics laboratory-developed libraries. Chromosomal abnormalities were analyzed using a bioinfomatics algorithm. RESULTS: A total of 464 cases were analyzed. The samples of 12 subjects had to be collected again because of a low fetal DNA fraction in the initially obtained samples. Among the 456 cases for which fetal genome results were obtained, 436 had a low risk of trisomy, 12 had a high risk for Down syndrome, two had a high risk for Edward syndrome, and four had sex chromosomal aneuploidy, showing that the positive percentage of chromosomal abnormalities was 4.4%. All 12 cases with high risk for Down syndrome were confirmed as having trisomy 21 by amniocentesis. CONCLUSIONS: Our laboratory-developed genomics-based NIPT showed high positive predictive value, therefore, NIPT may be replaced by our own developed method.

Neonatal Screening Tests for Inherited Metabolic Disorders using Tandem Mass Spectrometry: Experience of a Clinical Laboratory in Korea

BACKGROUND: The purpose of this study is to investigate the positive rates of screening tests for inherited metabolic disorders, set cutoff values, and report the actual status of internal quality controls in LabGenomics Clinical Laboratories by using LC-MS/MS system. METHODS: We use Agilent 1260 Infinity HPLC System (Agilent Technologies, USA) for liquid chromatography, and API 2000 (AB Sciex, Canada) for MS/MS system. We set up screening tests for 55 diseases, which include metabolic disorders of 25 amino acids, 16 organic acids, and 14 fatty acids. RESULTS: We determined the analyte cutoff values as 99.9 or 0.1 percentiles in 15,000 newborn samples. The total number of samples tested from January 2012 to September 2014 was 119,948; of these, 6,681 were repeated. Of the repeated samples, 713 were presumed to be positive in the screening tests. Repeat screening with newly obtained dried blood spot specimens was recommended for these 713 samples and 600 specimens were obtained. Thus, the recall rate was 0.5% (600/119,948) for all samples and 84.2% (600/713) for the samples presumed to be positive in the screening tests. About 70 samples, that is, 0.06% of the total samples and 11.7% of the "reobtained" samples, again tested positive; we recommended confirmatory tests for these samples. CONCLUSIONS: We have presented data on the status of neonatal screening tests for inherited metabolic disorders using LC-MS/MS, including positive rates and recall rates of screening tests, set up cutoff values and reported the actual status of internal quality controls in a clinical laboratory in Korea.

Evaluating the results of the Momguard noninvasive prenatal test

PURPOSE: To evaluate the performance of the Momguard noninvasive prenatal test by tracing the 'screen positive' results based on preliminary samples from Korean cohorts. MATERIALS AND METHODS: This preliminary study is based on data collected by the LabGenomics Clinical Laboratory (Seongnam, Korea) with informed consent. Only pregnant women who underwent both the Momguard test and karyotyping were included in this study. Momguard test results were compared with those of the karyotyping analysis. RESULTS: Among the 38 cases with 'screen positive' results by Momguard, 30 cases also had karyotyping results available. In three trisomy (T) 18 and three T13 cases, the Momguard results were concordant with the karyotyping results. For the T21 cases, except for one case belonging to the mid-risk zone, Momguard results from 23 out of 24 cases matched the karyotyping results. CONCLUSION: Momguard is a highly reliable screening tool for detecting T13, T18, and T21 cases in independent Korean cohort samples.

Performance of Momguard, a new non-invasive prenatal testing protocol developed in Korea

OBJECTIVE: To evaluate the performance of Momguard, non-invasive prenatal test (NIPT) for detecting trisomy (T) 21, T18, T13, and sex-chromosome abnormalities recently developed in Korea. METHODS: This preliminary study formed part of a large prospective cohort study conducted at Asan Medical Center, Seoul, Korea. Only pregnant women who underwent both NIPT and confirmatory karyotyping were included in this study. NIPT results were compared with those of karyotype analyses. RESULTS: Among 93 eligible cases, NIPT results could not be obtained in one case due to a low fetal cell-free DNA fraction. Based on NIPT, eight cases of fetal aneuploidies, including T21 (n=5), T18 (n=2), and T13 (n=1), were identified. For T21 and T18, the sensitivity and specificity of NIPT were both 100%, with a false-positive and false-negative rate of 0% and a positive-predictive value of 100%. One patient classified as having intermediate risk for T13 by NIPT was confirmed to have T13 by karyotyping, and there were no false-negative cases. No cases of sex-chromosome anomalies were detected by NIPT or karyotyping during the study period. CONCLUSION: Momguard is a reliable screening tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further prospective studies are necessary to confirm its utility.

Preoperative Erythropoietin Administration in Patients With Prostate Cancer Undergoing Radical Prostatectomy Without Transfusion

PURPOSE: In this study, we administered erythropoietin preoperatively to patients who underwent open radical prostatectomy without transfusion to increase their hemoglobin levels and investigated the efficacy of this procedure. MATERIALS AND METHODS: We evaluated 62 patients who underwent open radical prostatectomy performed by the same surgeon between June 2005 and January 2011. The 22 patients who refused transfusion were assigned to group 1; the patients who accepted transfusion were assigned to group 2. Before surgery, we administered erythropoietin beta to group 1 patients whose hemoglobin levels were <12 g/dL and retrospectively compared the clinical data of the two groups. We used the t-test and the chi-square test for statistical analysis. RESULTS: Mean preoperative hemoglobin levels in group 1 after erythropoietin administration (14.5 g/dL) were significantly higher than those in group 2 (13.59 g/dL, p=0.003). Moreover, the difference in the mean hemoglobin levels before and after surgery for group 1 patients (3.55 g/dL) significantly exceeded that for group 2 patients (2.08 g/dL, p=0.000). Additional analysis revealed no statistically significant differences in perioperative complications between the groups. CONCLUSIONS: Preoperative erythropoietin administration increased the safety margin of hemoglobin levels, and this strategy worked sufficiently well in our experience.

Primary Adenocarcinoma of the Rete Testis With Preceding Detection of Unilateral Hydronephrosis

Primary adenocarcinoma of the rete testis is a rare malignant testicular tumor with a poor prognosis. Here we report the case of a 54-year-old man with right hydronephrosis that was detected before the diagnosis of the primary testicular lesion. During the evaluation of the right hydronephrosis by use of abdominopelvic computed tomography, a painless, hard, solid lesion was found on the right testis. The patient underwent radical orchiectomy, and the pathologic examination revealed an adenocarcinoma of the rete testis. Multiple metastases were present at the time of diagnosis. The patient received combined chemotherapy after the surgery but lived only 8 months after the initial diagnosis.

Primary Adenocarcinoma of the Rete Testis With Preceding Detection of Unilateral Hydronephrosis

Primary adenocarcinoma of the rete testis is a rare malignant testicular tumor with a poor prognosis. Here we report the case of a 54-year-old man with right hydronephrosis that was detected before the diagnosis of the primary testicular lesion. During the evaluation of the right hydronephrosis by use of abdominopelvic computed tomography, a painless, hard, solid lesion was found on the right testis. The patient underwent radical orchiectomy, and the pathologic examination revealed an adenocarcinoma of the rete testis. Multiple metastases were present at the time of diagnosis. The patient received combined chemotherapy after the surgery but lived only 8 months after the initial diagnosis.

Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: The purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients. METHODS: A total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele. RESULTS: In the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (chi2=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele. CONCLUSION: The results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.

Efficacy of Periprostatic Anesthesia according to Lidocaine Dose during Transrectal Ultrasound-Guided Biopsy of the Prostate

PURPOSE: The aim of this study was to evaluate the efficacy of periprostatic lidocaine injection according to lidocaine dose during transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: The subjects of this study were 92 patients who had undergone transrectal ultrasound-guided 12-core biopsy of the prostate. The patients were randomly assigned to three groups: group 1 (n=31, no lidocaine injection), group 2 (n=30, periprostatic injection of 10 ml 1% lidocaine), and group 3 (n=31, periprostatic injection of 20 ml 1% lidocaine). The patients were assessed for pain by use of a 10-point visual analogue scale (VAS) and for other complications after the procedure. RESULTS: The mean VAS scores of groups 1 through 3 were 0.93+/-0.89, 1.32+/-1.37, and 1.13+/-1.10, respectively. There were no statistically significant differences between the three groups. However, the mean VAS score of the biopsy pain was 5.0+/-1.48, 3.93+/-1.94, and 3.60+/-2.15, in the same groups, respectively, with statistically significant differences between group 1 and the other groups. Patients in groups 2 and 3 reported significantly less biopsy pain than did group 1 patients (p=0.004, 0.021), with no statistically significant difference in VAS score between groups 2 and 3 (p=0.533). With respect to post-biopsy complications, there were no significant differences in the incidence of hematuria, hematospermia, rectal bleeding, or infection among the three groups. CONCLUSIONS: Periprostatic injection of local anesthesia with lidocaine was associated with significantly less pain than in the absence of anesthesia. Furthermore, a 20-ml dose of lidocaine produced no better pain control than did a 10-ml lidocaine dose for prostate biopsy.

Efficacy of Periprostatic Anesthesia according to Lidocaine Dose during Transrectal Ultrasound-Guided Biopsy of the Prostate

PURPOSE: The aim of this study was to evaluate the efficacy of periprostatic lidocaine injection according to lidocaine dose during transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: The subjects of this study were 92 patients who had undergone transrectal ultrasound-guided 12-core biopsy of the prostate. The patients were randomly assigned to three groups: group 1 (n=31, no lidocaine injection), group 2 (n=30, periprostatic injection of 10 ml 1% lidocaine), and group 3 (n=31, periprostatic injection of 20 ml 1% lidocaine). The patients were assessed for pain by use of a 10-point visual analogue scale (VAS) and for other complications after the procedure. RESULTS: The mean VAS scores of groups 1 through 3 were 0.93+/-0.89, 1.32+/-1.37, and 1.13+/-1.10, respectively. There were no statistically significant differences between the three groups. However, the mean VAS score of the biopsy pain was 5.0+/-1.48, 3.93+/-1.94, and 3.60+/-2.15, in the same groups, respectively, with statistically significant differences between group 1 and the other groups. Patients in groups 2 and 3 reported significantly less biopsy pain than did group 1 patients (p=0.004, 0.021), with no statistically significant difference in VAS score between groups 2 and 3 (p=0.533). With respect to post-biopsy complications, there were no significant differences in the incidence of hematuria, hematospermia, rectal bleeding, or infection among the three groups. CONCLUSIONS: Periprostatic injection of local anesthesia with lidocaine was associated with significantly less pain than in the absence of anesthesia. Furthermore, a 20-ml dose of lidocaine produced no better pain control than did a 10-ml lidocaine dose for prostate biopsy.

Initial Biopsy Outcome Prediction in Korean Patients-Comparison of a Noble Web-based Korean Prostate Cancer Risk Calculator versus Prostate-specific Antigen Testing

We developed and validated a novel Korean prostate cancer risk calculator (KPCRC) for predicting the probability of a positive initial prostate biopsy in a Korean population. Data were collected from 602 Koreans who underwent initial prostate biopsies due to an increased level of prostate-specific antigen (PSA), a palpable nodule upon digital rectal examination (DRE), or a hypoechoic lesion upon transrectal ultrasound (TRUS). The clinical and laboratory variables were analyzed by simple and multiple logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was computed to compare its performance to PSA testing alone. Prostate cancer was detected in 172 (28.6%) men. Independent predictors included age, DRE findings, PSA level, and prostate transitional zone volume. We developed the KPCRC using these variables. The AUC for the selected model was 0.91, and that of PSA testing alone was 0.83 (P < 0.001). The AUC for the selected model with an additional dataset was 0.79, and that of PSA testing alone was 0.73 (P = 0.004). The calculator is available on the website: http://dna.korea.ac.kr/PC-RISC/. The KPCRC improved the performance of PSA testing alone in predicting the risk of prostate cancer in a Korean population. This calculator would be a practical tool for physicians and patients.

Cystic Dysplasia of the Rete Testis Accompanying an Inguinal Hernia: A 63-Year-Old Man

Cystic dysplasia of the rete testis (CDT) is a very rare congenital benign testicular tumor that is often associated with ipsilateral genitourinary anomalies. It is usually found in the pediatric population and must be differentially diagnosed from a malignant lesion. Here we report the case of a 63-year-old man with a left inguinal hernia who visited our urologic outpatient clinic. Scrotal ultrasonography showed a left direct inguinal hernia in the inguinal area and a well-circumscribed cystic lesion containing multiple minute cysts with echogenic foci occupying almost one-third of the left testicular parenchyma. Testicular tumor markers were within the normal range and a computed tomography scan of the abdomen showed no genitourinary abnormalities. We presumed that the left testicular lesion was malignant, and the patient underwent radical orchiectomy. However, the pathologic examination revealed a CDT. Here we present this case of a 63-year-old man with an inguinal hernia accompanied by multiple cystic lesions on the left testis.

Genetic Polymorphism of FLG in Korean Ichthyosis Vulgaris Patients

BACKGROUND: Filaggrin is a key protein that facilitates the formation of skin barrier by forming a stratum corneum. Mutations in the gene encoding filaggrin (FLG) have recently been reported in patients with ichthyosis vulgaris (IV). Interestingly, there are ethnic differences between FLG mutations identified in Asians and Europeans, and few FLG mutations are overlapping between Chinese and Japanese IV patients. OBJECTIVE: The aim of this study was to investigative the genetic polymorphism of FLG in Korean IV patients. METHODS: Genomic DNA was extracted from whole venous blood specimen of Korean patients with IV and a control group, and the full sequence of FLG was determined via overlapping long-range polymerase chain reaction method. RESULTS: Analysis of base sequence previously unreported reveal new nonsense mutation p.Y1767X in a Korean IV patient, and additional new single nucleotide polymorphisms. CONCLUSION: On the basis of this study, it is anticipated that analysis of FLG gene sequence be extended to other dermatoses associated with FLG, such as atopic dermatitis.

Gender-Specific Association of the Brain-Derived Neurotrophic Factor Gene with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Brain-derived neurotrophic factor (BDNF), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, could play a role in ADHD development. We aimed to explore the relationships between ADHD and BDNF gene polymorphism. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test on 151 trios, and compared the results of a continuous performance test (CPT) according to the genotype of the three single nucleotide polymorphisms (rs11030101, rs6265, rs16917204) in the BDNF gene. RESULTS: In the case-control analysis, the AA genotype of the BDNF rs11030101 polymorphism was significantly associated with ADHD only in girls (p=0.024, odds ratio=3.00). The T-G-G haplotype was significantly less frequent (p=0.005) and A-G-G was more frequent (p=0.048) in girls with ADHD than in control girls (global p=0.027). A multivariate analysis of variance for commission errors on the CPT showed a significant main effect for the rs11030101 genotype (p=0.026) and an interaction effect of the rs11030101 genotype and gender (p=0.032) in ADHD probands. CONCLUSION: These results provide preliminary evidence for a gender-specific association between BDNF and ADHD in the Korean population.