• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2625-2628
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• 2016

ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (${\Delta}27$) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and ${\Delta}27$ was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.116-120
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• 2016

Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively. We report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth, because of hypoglycemia. Investigations revealed hypoglycemia with hyperinsulinemia, but no ketone bodies, and a low level of free fatty acids. High dose glucose infusion, enteral feeding, and medications could not maintain the patient's serum glucose level. Genetic testing revealed a new variation of ABCC8 mutation. Therefore, we report this case of CHI caused by a novel mutation of ABCC8 in a half-Korean newborn infant with diazoxide-unresponsive hyperinsulinemic hypoglycemia.

• Genomics & Informatics
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• v.11 no.4
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• pp.254-262
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• 2013

The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p=0.0057) and the GG genotype (61.0% vs. 39.7%, p=0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p=0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4659-4664
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• 2015

Background: ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. TC/CC: OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

• Clinical and Experimental Pediatrics
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• v.58 no.8
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• pp.309-312
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• 2015

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium ($K_{ATP}$) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the $K_{ATP}$ channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

• Neonatal Medicine
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• v.28 no.2
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• pp.94-98
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• 2021

Neonatal diabetes mellitus (NDM) is a rare disease that occurs at less than 6 months of age and is presumably caused by a mutation in the gene that affects pancreatic beta-cell function. Approximately 80% of NDM cases reveal a known genetic mutation, and mutations in potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) and ABCC8 affecting the pancreatic beta-cell adenosine triphosphate-sensitive potassium channel may be treated with oral sulfonylurea. Early recognition of mutations in KCNJ11 and ABCC8 is important because early administration of sulfonylurea can not only control blood glucose levels but also improve neurodevelopmental outcomes. In the present study, we report a case of NDM that initially presented as diabetic ketoacidosis at the age of 1 month, accompanied by seizures during hospitalization. After confirmation of the KCNJ11 gene mutation (c.989A>C), we started administering oral sulfonylurea (glimepiride) at the age of 2 months. After gradually increasing the dosage of glimepiride, insulin was discontinued at the age of 3 months. To date, the infant's blood glucose levels have been well controlled without significant hypoglycemic events. No further episodes of seizures have occurred, and his developmental status is favorable.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.431-436
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• 2008

To identify genes whose expression correlated with biological features of therapy-related AML (t-AML), we analyzed the expression profiles of de novo AML t(9;11) and t-AML t(9;11) bone marrow samples using previously published SAGE data. Three-hundred twenty-nine transcripts that satisfied statistical (P<0.05) and magnitude-of-change ($\geq$ 4-fold) criteria were identified as differentially expressed between de novo AML t(9;11) and t-AML t(9;11) cells. Of these transcripts, 301 (91%) matched known genes or ESTs and were classified according to functional categories (http://david.abcc.ncifcrf.gov/). The majority of differentially expressed genes in t-AML t(9;11) were involved in the regulation of biological and metabolic processes. Especially prominent among these were genes related to immune and drug responses. These results establish a framework for developing new drugs for the treatment of t-AML.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.139-160
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• 2004

The obesity is detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms(SNPs), some of which promote the development of obesity-related type 2 diabetes mellitus. Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. In this review, five major conclusions are reached: (1)To be clinically significant, SNPs must be relevant, prevalent, modifiable, and measurable. (2)Differences in SNPs may have been caused by famine, ultraviolet light, alcohol, climate, agricultural revolution. livestock, lactase persistence, and westernized lifestyle. (3)Candidate obesity genes of calorie intake restriction are SIM 1, MC3R, MC4R, AGRP, CART, CCK, CNTFR, DRD2, Ghrelin, 5-HT receptor, NPY, PON and those of energy metabolism are LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, PGC-1, Androgen receptor and those of fat mobilization are AGT, ACE, ADA, APM1, Apolipoproteins, PPAR, FABP, FOXC2, GCGR, $11-{\beta}HSDI$, LDLR, Hormonal sensitive lipase, Perilipin, $TNF-{\alpha}$, $TNF-{\beta}$ (4)Candidate obesity genes in the eastern are NPY, LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, ACE, APM1, PPAR, and FABP. (5)Candidate obesity genes in type 2 diabetes mellitus are MC3R, MC4R, B2AR, B3AR, ADA, APM1, PPAR, FABP, FOXC2, PC1, PC2, ABCC8, CAPN10, CYP19, CYP7, ENPP1, GCK, GYS1, IGF, IL-6, Insulin receptor, IRS, and LPL. The discovery of SNPs will lead to a greater understanding of the pathogenesis of obesity and to better diagnostics, treatment, and eventually prevention.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.185-197
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• 2003

This study was performed to identify the characteristics of the OFC1 gene (locus: chromosome 6p24.3) in Korean patients, which is assumed to be the major gene behind the nonsyndromic cleft lip and palate. The sample consisted of 80 subjects: 40 nonsyndromic cleft lip and palate patients (proband, 20 males and females, mean age 14.2 years); and 40 normal adults (20 males and 20 females, mean age 25.6 years). Using PCR-based assay, the OFC1 gene was amplified, sequenced, and then searched for similar protein structures. Results were as follows: 1. The OFC1 gene contains the microsatellite marker 'CA' repeats. The number of the reference 'CA' repeats was 21 times, and formed as TA(CA)11TA(CA)10. But, in Koreans, the number of tandem 'CA' repeats was varied from 17 to 26 except 18, and 'CA' repeats consisted of TA(CA)n. 2. Nine allelic variants were found. Distribution of the OFC1 allele was similar between the patients and control group. 3. There was a replacement of the base 'T' to 'C' after 11 tandem 'CA' repeats in Koreans compared with Weissenbach's report. However, the difference did not seem to be the ORF prediction results between Koreans and Weissenbach's report. 4. The BLAST search results showed the Telomerase reverse transcriptase (TERT) and the Nucleotide binding protein 2 (NBP2) as similar proteins. The TERT was a protein product by the hTERT gene in the locus 5p15.33 (NCBI Genome Annotation; NT023089) The NBP2 was a protein product by the ABCC3 (ATP-binding cassette, sub-family C) gene in the locus 17q22 (NCBI Genome Annotation; NT010783). 5. In the Pedant-Pro database analysis, the predictable protein structure of the OFC1 gene had at least one transmembrane region and one non-globular region.