Five patients with 11β-hydroxylase deficiency due to CYP11B1 gene mutation: A case study / 中华内分泌代谢杂志

Objective:To investigate the clinical and molecular characteristics of 11β-hydroxylase deficiency(11β-OHD) to improve the understanding of this disorder.Methods:The clinical manifestation, hormone level, imaging examination, characteristics of gene variation and follow-up of five patients with 11β-OHD diagnosed in Henan Children′s Hospital from 2016 to 2021 were carefully reviewed.Results:Among the 5 children, 3 were male and 2 were female, all without positive family history. The age at diagnosis was 1 year 5 months to 7 years(average 3 years and 9 months), and the bone age was 3 years 6 months to 16 years(average 10 years and 3 months). Two cases were misdiagnosed as 21-hydroxylase deficiency(21-OHD) and treated with long-term mineralocorticoids. Three patients presented with hypertension and one patient had testicular adrenal rest tumor. Adrenal CT showed bilateral adrenal hyperplasia in five patients. ACTH, 17-hydroxyprogesterone, testosterone, and androstenedione levels were increased in 5 children, and hypokalemia occurred in 1 patient. One patient carried homozygous novel missense variant, and four patients had compound heterozygous variants. Four patients carried missence mutations, two patients had deletion and one patient harbored a chimeric CYP11B2 exon1-6/CYP11B1 exon7-9. Three novel CYP11B1 mutations, including c. 1385T>C(p.L462P), c.64C>T(p.Q22*)and c. 1354G>A(p.G452R) were identified. The final height of 2 male children were 164.4 cm and 150.2 cm, respectively, and the related hormone levels of the other 3 children were normal.Conclusion:11β-OHD is easily misdiagnosed, leading to severe impairment of final height. CYP11B1 gene variation is complex and diverse, which requires variety of gene detection methods.

The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population

ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

Mutation analysis and phenotypic investigation in patients with primary distal renal tubular acidosis / 中华肾脏病杂志

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Renal Tubular Acidosis Presenting as Nephrogenic Diabetes Insipidus

Background: Nephrogenic diabetes insipidus (DI) can be primary or secondary to variouscauses. Case Characteristics: One child with Fanconi syndrome with proximal renaltubular acidosis (RTA) due to nephropathic cystinosis, and other with Distal RTA withhearing loss. Observation: Both cases showed features of nephrogenic DI, which resolvedafter treating the primary pathology. Message: Renal Tubular acidosis may causenephrogenic DI.

Analysis of clinical manifestations and gene mutations of 13 child patients with rare causes of primary adrenal insufficiency / 中华内分泌代谢杂志

Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female) was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation,electrolyte imbalance/salt-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NR0B 1 gene (9/13),ABCD 1 gene (3/13),and CYP 11A 1 gene (1/13).NR0B1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics.CYP11A1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/sah-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.

Study on Relationships of Gene Polymorphism of MTRR and SLCO1B1 with Blood Concentration of MTX and HD-MTX- induced ADR in ALL Children / 中国药房

OBJECTIVE： To study the relationships of polymorphism of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus with drug concentration of methotrexate （MTX） and high-dose MTX （HD-MTX）-induced ADR in acute lymphoblastic leukemia （ALL） children. METHODS： From Oct. 2015 to Sept. 2018， 70 ALL hospitalized children of Han nationality in Sichuan area who received HD-MTX treatment and were in consolidation chemotherapy were selected retrospectively from Sichuan People’s Hospital. The blood concentration of MTX at 48 and 72 hours after administration was measured by EMIT. The genetic typing of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus were detected with real-time PCR. The relationships of the polymorphism of MTRR gene and SLCO1B1 gene with MTX blood concentration [dose-corrected concentration （c48 h/D，48 h）， the proportion of children with different concentration of MTX （≤0.1， ＞0.1 μmol/L）] and ADR （such as myelosuppression， liver function damage， gastrointestinal response， mucosal damage， rash， etc.） were analyzed. Binary Logistic regression analysis for the correlation of ADR with different influencing factors （gene polymor- phism， blood concentration of MTX， immunophenotyping， body mass index， etc.） was carried out by Wald method. RESULTS： Totally 31， 32， 7 children with MTRR gene AA， AG and GG genotype， while 23， 37， 10 children with SLCO1B1 gene TT， TC and CC genotype were detected. The distribution of each genotype in 70 children conformed to Hardy-Weinberg equilibrium （P＞0.05）. There was no significant difference in c48 h/D（48 h） of children and the proportion of children with different concentration of MTX （72 h） among difterent genotypes of MTRR and SLCO1B1 gene （P＞0.05）. There was statistical significance in the incidence of liver function injury in children with different genotypes of MTRR gene （P＜0.05）， and the AA genotype was significantly higher than the AG+GG genotype （P＜0.05）. There was no correlation of MTRR gene polymorphism with the incidence of other ADR， neither SLCO1B1 gene polymorphism with the incidence of ADR （P＞0.05）. The results of Binary Logistic regression analysis showed that liver function damage in ALL children was related to the gene polymorphism of MTRR； gastrointestinal reaction was related to whether the plasma concentration was more than 0.1 μmol/L at 72 h； mucosal damage was related to the immune type and BMI of children； the occurrence of skin allergy was correlated with body weight of children（P＜0.05）. CONCLUSIONS： Gene polymorphism of MTRR rs1801394 locus may associated with the occurrence of HD-HTX-induced liver function injury in ALL children， but its polymorphism and gene polymorphism of SLCO1B1 rs11045879 locus are not related to MTX blood concentration in ALL children.

Vitamin D Dependent Rickets Type 1A Caused by CYP27B1 Mutation

Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in CYP27B1 . Clinical findings are growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets. We aimed to present the VDDR1A case with a genetic study of CYP27B1 . The 14-month-old boy was admitted to the hospital due to a seizure. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25(OH) vitamin D, and 1,25(OH)2 vitamin D values were 5.1 mg/dL, 3.7 mg/dL, 705 IU/L, 429 pg/mL, 24.9 ng/mL, and 8.8 pg/mL, respectively. Radiological study showed cupping and fraying of the distal ulna and radius. The molecular genetic study revealed that the patient had a compound heterozygous mutation, Phe443Profs*24 and c.589+1G>A, in CYP27B1 . Genetic analysis of the family members presented that the mother was heterozygous for the mutation c.589+1G>A, and that the father was heterozygous for Phe443Profs*24. The patient was treated with calcium lactate and calcitriol. Until now, six Korean patients with VDDR1A have been studied. Including this case, Korean patients with VDDR1A were found to have only three different mutations in 14 alleles, indicating that the mutation in the CYP27B1 gene is homogeneous in the Korean population.

Testicular microlithiasis in a boy with X-linked adrenal hypoplasia congenita

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up.

The clinical manifestations and genetic analysis of lisencephaly in children / 临床儿科杂志

Objective To explore clinical characteristics and pathogenic gene of lisencephaly. Methods The clinical manifestation, laboratory examination and gene detection results of lisencephaly in two children were analyzed retrospectively, and relevant literature were reviewed. Results Two male children with lisencephaly are at ages of 7 months, and 3 years and 4 months respectively. Both of them were admitted to hospital due to epilepsy and loss of consciousness at the time of attack. There was no obvious abnormality in laboratory examination. Both of their EEG indicated epileptic wave. Cranial MRI showed lissencelphaly. Gene analysis showed that there was a heterozygous mutation of IVS3-1G>A in PAFAH1B1 gene in a child, which resulted in the deletion of exon 4 in mRNA level by functional analysis. No mutations were found in the parents of the child. The other one had c.274A>G mutation (p.K92E) in PAFAH1B1 gene, which has not been reported before, and his parents were normal. Conclusion Patients with lissencelphaly may combine with epilepsy, and the PAFAH1B1 gene mutation is the common cause.

Establishment of allele-specific real-time polymerase chain reaction for detecting neonatal hyperbilirubinemia related gene SLCO1B1 A388G polymorphism / 中华实用儿科临床杂志

Objective To establish the allele-specific real-time polymerase chain reaction (ASPCR) for detection of neonatal hyperbilirubinemia related gene SLCO1B1 A388G polymorphism and apply this assay to identify the clinical samples.Methods According to SLCO1B1 A388G polymorphism loci,specific primers were designed and the assay was established.Wide type plasmid and mutant plasmid were constructed.Fifty clinical samples were selected,including 30 samples of neonatal hyperbilirubinemia that had been diagnosed with SLCO1B1 A388G mutant and 20 samples of healthy newborns without SLCO1B1 A388G mutant were selected as the controls.Wide type plasmid,mutant plasmid and clinical samples were tested by specific and non-specific primers.A388G polymorphism was determined by difference in Ct (cycle threshold) between specific and non-specific primers.Then,the accuracy,sensitivity and specificity of assay were evaluated.Results The difference in Ct (cycle threshold) between specific and non-specific primers that amplified equivalent wide type template was 13.97 ±0.75.The assay could correctly distinguish the wide type and mutant plasmid.Probit regression analysis showed the sensitivity of the assay could reach to 5.28 copies/μL.For clinical samples,the Ct values of the samples with A388G mutation was less than 37.75 and showed positive results,while the samples without A388G mutation did not show any amplification nor Ct values were larger than 37.75,which showed negative results.Conclusions ASPCR is a fast,simple and effective method for SLCO1B1 A388G polymorphism detection of the clinical simples.It can be used for large sample screening for neonatal hyperbilirubinemia gene loci.

Association of SH2B1 gene polymorphism with overweight and obesity / 中华内分泌代谢杂志

To investigate the association of SH2B1 gene rs7359397 polymorphism with overweight and obesity,as well as some related metabolic indicators in Northwest Chinese. Based on the cohort of China National Diabetes and Metabolic disorders Study(2007-2008) in Shanxi province, totally 1210(including 635 overweight and 167 obese) males and 1711(including 781 overweight and 212 obese) females were participated in this study. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry( MALDI-TOF MS) was adopted as the genotyping method. After adjusting for age, the single nucleotide polymorphism rs7359397 of SH2B1 was found to be associated with overweight and obesity in males. The correlation with overweight accords with the dominant(P=0. 02), overdominant(P=0. 03), and log-additive models(P=0. 025), while the correlation with obesity accords with the dominant(P=0. 0078), overdominant(P=0. 0081), and log-additive models(P=0. 015). rs7359397 showed to have a significant association with body mass index, body fat percentage, fasting serum insulin, homeostasis model assessment of insulin resistance in males;and high density lipoprotein-cholesterol in females(P<0. 05). The results show that SH2B1 rs7359397 polymorphism is associated with overweight, obesity, and related metabolic indicators in males of the population studied.

Analysis of Dyslipidemia Correlation and Polymorphisms of ApoE and SLCO1B1 Gene in Dyslipidemia People / 现代检验医学杂志

Objective To investigate the frequency distribution of ApoE and SLCO1B1 genotypes in abnormal blood lipid lev-els in Xiangya Hospital,explore the correlation of ApoE and SLCO1B1 genotypes with various indicators of dyslipidemia,and provide evidence for prevention and treatment of atherosclerotic diseases.Methods Blood lipid data including TG,TC,LDL-C and HDL-C in 87 cases of dyslipidemia people in Xiangya Hospital from June in 2016 to April in 2017 were collected.The ApoE and SLCO1B1 genotypes were detected by PCR fluoroscopy in 87 cases of dyslipidemia.The distribution of gene fre-quency was analyzed and the differences of blood lipid indexes among the genotypes were compared.Results The frequen-cies of each ApoE genotype in 87 cases of dyslipidemia were E2/E2 1.15%,E2/E3 13.79%,E2/E4 1.15%,E3/E3 56.32%,E3/E4 26.44% and E4/E4 1.15%,respectively.The highest proportion of allele frequency was E3 with the per-cent of 76.44%,E2 and E4 occupied 8.62% and 14.94%,respectively.The concentration of LDL-C in E4 phenotype group was higher than that in E2 group and E3 group,and there was no significant difference in the levels of TG,TC,LDL-C and HDL-C.The frequencies of each SLCO1B1 genotype were *1a/*1a 6.90%,*1a/*1b 36.70%,*1a/*15 13.79%,*1b/*1b 26.44% and *1b/*15 16.09%.The highest frequency of each haplotype was *1b with the percent of 52.87%,*1a and *15 occupied 32.18% and 14.94%,respectively,and no * 5 type was detected.There were no significant differ-ences in TG,TC,LDL-C and HDL-C concentrations between SLCO1B1 groups.Conclusion ApoE gene frequency distribu-tion was uneven.Its polymorphism be related with the lipid levels.The frequency distribution of SLCO1B1 gene had racial differences,and its polymorphism was not related with lipid level.According to the the genotypes of ApoE and SLCO1B1, clinician can choose the right dose of drug to prevent coronary atherosclerotic disease.

Meta-Analysis of the SLCO1B1 c.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins

BACKGROUND: Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS: We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I 2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS: No significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS: No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.

Optimización de la Reacción en Cadena de la Polimerasa para la Detección del gen B1 de T. gondii / Optimization of Polymerase Chain Reaction for the detection of the B1 gene of T. gondii

Optimizar las condiciones de amplificación del gen B1 (35 copias en el genoma) para la detección de ADN de T.gondii en casos probables de toxoplasmosis cerebral. Materiales y métodos: Se realizó extracción de ADN a partir de exudado peritoneal de ratones inoculados con la cepa RH de T. gondii obteniendo 17 ml con una concentración inicial de 1x107 parásitos/ml. Se optimizaron las condiciones de PCR del gen B1. Resultados: Se obtuvo amplificación de un fragmento de 132 pb a partir de ADN obtenido de diluciones seriadas desde 1x106 a 1x10-1 parásitos por ml, estableciéndose un límite de detección de 1 taquizoíto de T. gondii...

This study aimed at optimizing the amplification conditions of the B1 gene (35 copies in the ge­nome) of T. gondii in cases of possible brain toxoplasmosis. Materials and methods: DNA was extracted from the peritoneal exudate of mice inoculated with the RH strain of T. gondii. Total exudate volume was 17 mL with a concentration of 1x107 parasites/mL. PCR conditions for the B1 gene were further optimized.Results: Serial dilutions from 1x106 to 1x10-1 parasites/mL were needed for amplifying a fragment of 132 bp . This set the detection limit for 1 T. gondii tachyzoite...

Progress of SF3B1 gene mutation and hematological malignancies / 国际儿科学杂志

The SF3B1 gene encodes subunit 1 of the splicing factor 3b,which is a core component of the U2 small nuclear ribonucleoprotein and plays an important role in the process of RNA splicing. Abnormal splicing caused by SF3B1 mutations are associated with hematological malignancies,particularly with myelodys-plastic syndrome,refractory anemia with ring sideroblasts associated with marked thrombocytosis and chronic lymphocytic leukemia( CLL) . In myelodysplastic syndrome and refractory anemia with ring sideroblasts associat-ed with marked thrombocytosis,SF3B1 mutations are bond up with favorable prognosis and strongly with ring sideroblasts. But in CLL,SF3B1 mutations are factors of poor prognosis.

Association between polymorphism of ATP2B1 gene,its interaction with smoking and essential hypertension--a case-control study / 中华流行病学杂志

Objective To investigate the association between polymorphism of ATP2B1 gene,its interaction with smoking and susceptibility of essential hypertension. Methods A case-control study was conducted to elucidate the role of ATP2B1 gene variants related to the risk of essential hypertension. Genomic DNA was extracted from peripheral blood leukocytes,using the QIAamp DNA Mini Kit(QIAGEN,Germany). Two SNPs,-rs17249754 and rs6253,were examined on 1 280 patients and 1 010 healthy controls,using a Snapshot method. Statistical analyses were performed with SPSS Windows software(version 19.0;SPSS,Chicago,IL). Results A significant difference was found in rs17249754 allele frequency between cases and controls(OR=1.223,95%CI:1.083-1.381,P=0.001). After adjustment for age,sex,BMI,smoking and drinking,the difference was still statistically significant(OR=1.212,95%CI:1.070-1.373,P=0.003). In addition,data from genotype distribution analysis under different models showed that appeared significant associations between ATP2B1 gene polymorphism and essential hypertension(additive model OR=1.469,95%CI:1.121-1.925,P=0.005;dominant model OR=1.324,95%CI:1.029-1.704,P=0.029;recessive model OR=1.123,95%CI:1.031-1.223,P=0.008). In this study,the proportion of smokers in cases was significantly higher than that in controls(P=0.005),but no associations between rs17249754-smoking interaction and essential hypertension were found after the adjustment for gender,age,BMI and alcohol consumption (OR=1.024,95%CI:0.614-1.707). Conclusion Our research findings showed that the polymorphism of ATP2B1 gene rs17249754 was significantly associated with the incidence of essential hypertension in Han population of northeastern China. However,the interaction between rs17249754 and smoking did not seem to have contributed to the occurrence of the essential hypertension.

Association between polymorphism of ATP2B1 gene,its interaction with smoking and essential hypertension--a case-control study / 中华流行病学杂志

Objective To investigate the association between polymorphism of ATP2B1 gene,its interaction with smoking and susceptibility of essential hypertension. Methods A case-control study was conducted to elucidate the role of ATP2B1 gene variants related to the risk of essential hypertension. Genomic DNA was extracted from peripheral blood leukocytes,using the QIAamp DNA Mini Kit(QIAGEN,Germany). Two SNPs,-rs17249754 and rs6253,were examined on 1 280 patients and 1 010 healthy controls,using a Snapshot method. Statistical analyses were performed with SPSS Windows software(version 19.0;SPSS,Chicago,IL). Results A significant difference was found in rs17249754 allele frequency between cases and controls(OR=1.223,95%CI:1.083-1.381,P=0.001). After adjustment for age,sex,BMI,smoking and drinking,the difference was still statistically significant(OR=1.212,95%CI:1.070-1.373,P=0.003). In addition,data from genotype distribution analysis under different models showed that appeared significant associations between ATP2B1 gene polymorphism and essential hypertension(additive model OR=1.469,95%CI:1.121-1.925,P=0.005;dominant model OR=1.324,95%CI:1.029-1.704,P=0.029;recessive model OR=1.123,95%CI:1.031-1.223,P=0.008). In this study,the proportion of smokers in cases was significantly higher than that in controls(P=0.005),but no associations between rs17249754-smoking interaction and essential hypertension were found after the adjustment for gender,age,BMI and alcohol consumption (OR=1.024,95%CI:0.614-1.707). Conclusion Our research findings showed that the polymorphism of ATP2B1 gene rs17249754 was significantly associated with the incidence of essential hypertension in Han population of northeastern China. However,the interaction between rs17249754 and smoking did not seem to have contributed to the occurrence of the essential hypertension.

Medullary Sponge Kidney Detected in the Pediatric Age

PURPOSE: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilatation of precalyceal collecting tubules. MSK incidence and prevalence in the general population is uncertain and only a few patients are reported especially in the pediatric age. There has been increasing reports of patients with MSK who have other malformative disorders. Also several case reports concerning about etiological association of some genes. METHODS: Collaborative study through nation-wide survey was done to investigate the incidence and etiological association of some genes such as GDNF gene, ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children. RESULTS: Four cases of MSK who have various other malformative disorders were collected. There are no mutations of GDNF gene, ATP6V1B1, ATP6V0A4 gene in all patients. CONCLUSION: MSK is one of the very rare diseases in pediatric age. The etiological association of GDNF gene , ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children is not proved.

Serologic Survey of Toxoplasmosis in Seoul and Jeju-do, and a Brief Review of Its Seroprevalence in Korea

Knowledge of the prevalence of human Toxoplasma gondii infection is required in the Republic of Korea. In this study, we surveyed the seroprevalence of T. gondii infection and analyzed the risk factors associated with seropositivity among residents in 2 administrative districts; Seoul and the island of Jeju-do, which have contrasting epidemiologic characteristics. Sera and blood collected from 2,150 residents (1,114 in Seoul and 1,036 in Jeju-do) were checked for IgG antibody titers using ELISA and for the T. gondii B1 gene using PCR. In addition, participants completed a questionnaire that solicited information on gender, age, occupation, eating habits, history of contact with animals, and travel abroad. The T. gondii B1 gene was not detected in all residents examined. However, ELISA showed 8.0% (89 of 1,114 sera) positive for IgG antibodies against T. gondii in Seoul and 11.3% (117 of 1,036 sera) in Jeju-do. In both districts, the positive rates were higher in males than in females, and those 40-79 years of age showed higher rates than other ages. In Seoul, residents older than 70 years of age showed the highest positive rate, 14.9%, whereas in Jeju-do the highest prevalence, 15.6%, was in those in their sixties. The higher seropositive rate in Jeju-do than in Seoul may be related to eating habits and occupations. The present results and a review of related literature are indicative of an increased seroprevalence of T. gondii in Korea in recent years.

Benign Recurrent Intrahepatic Cholestasis with a Single Heterozygote Mutation in the ATP8B1 Gene / 대한소아소화기영양학회지

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive inherited disorder characterized by multiple recurrent episodes of severe cholestatic jaundice without obstruction of extrahepatic bile duct. We present the case of a 7-year-old boy with BRIC confirmed by mutation analysis in the ATP8B1 gene and typical clinical manifestation. Despite inheritance of BRIC, we detected a mutation on only one allele. To our knowledge, this is the first report of BRIC with a confirmed single heterozygote novel mutation in the ATP8B1 gene in Korea.