Effects of Transplantation with Marrow-Derived Mesenchymal Stem Cells Modified with Survivin on Renal Ischemia-Reperfusion Injury in Mice

Purpose

To determine whether renal injury induced by ischemia-reperfusion (I/R) could be further improved by mesenchymal stem cells (MSCs) modified with survivin.

Materials and Methods

Lentiviral vectors were used to introduce the survivin gene into MSCs and the MSCs modified with survivin were transplanted into established mice models of renal I/R injury. Seven days later, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured and the survival of MSCs was determined. Hematoxylin and eosin staining was used to assess renal pathological change. The expressions of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) in kidney tissue were detected by western blot.

Results

Mice transplanted with survivin-modified MSCs demonstrated good renal function recovery with Scr and BUN decline close to normal levels and improvement of renal I/R injury repair. Additionally, the survival of transplanted MSCs modified with survivin was enhanced and the expression of HGF and bFGF in kidney tissue was increased.

Conclusion

Our results demonstrated that MSCs engineered to over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increased production of protective cytokines in ischemic tissue.     

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

OBJECTIVE:

To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice.

METHODS:

Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson''s trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR.

RESULTS:

Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3).

CONCLUSION:

Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.     

Genistein ameliorates parathyroid hormone-induced epithelial-to-mesenchymal transition and inhibits expression of connective tissue growth factor in human renal proximal tubular cells

Introduction

Genistein, a soybean and soy-based product, has been reported to inhibit the growth of a wide range of cancer cells, but there is no evidence concerning its treatment of chronic kidney disease. The aim was to investigate whether genistein has potential to inhibit parathyroid hormone (PTH)-induced renal interstitial fibrosis.

Material and methods

Using human renal tubular epithelial HK-2 cells, α-smooth muscle actin (α-SMA) was assessed by using immunofluorescence detection. α-Smooth muscle actin, E-cadherin and connective tissue growth factor (CTGF) were measured by Western blot analysis. The promoter activity of the CTGF gene was examined by the luciferase reporter assay.

Results

When cells were treated with PTH (0.1 nM) for 48 h, α-SMA protein expression was induced significantly, the protein expression of E-cadherin decreased substantially, and the promoter activity of the CTGF gene as well as its mRNA and protein expression levels increased (p < 0.01). Interestingly, genistein effectively inhibited PTH-induced α-SMA expression, restored E-cadherin expression, decreased mRNA and protein expression of CTGF, and suppressed the promoter activity of CTGF in a dose-dependent manner.

Conclusions

Genistein has the ability to block the biomarker for renal transdifferentiation and epithelial-to-mesenchymal transition, α-SMA, following PTH treatment and inhibit CTGF expression in human renal tubular epithelial cells; these might be important modes of actions that contribute to genistein anti-fibrogenic effects and may have great implications for its potential in clinical treatment of renal interstitial fibrosis.     

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients

Purpose

Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN).

Materials and Methods

Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function.

Results

Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years.

Conclusion

In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.     

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B

Background/Aims

Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.

Methods

The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.

Results

Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.

Conclusions

Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.     

Fluoxetine protects against big endothelin-1 induced anti-apoptosis by rescuing Kv1.5 channels in human pulmonary arterial smooth muscle cells

Purpose

Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. Previous studies have shown that fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulates Kv1.5 channels, subsequently promoting apoptosis in human PASMCs cultured in vitro.

Materials and Methods

Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and expression of TRPC1 and Kv1.5 were detected.

Results

In the ET-1 induced group, the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and anti-apoptosis, which was reversed when treated with fluoxetine. The decreased expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting proliferation while promoting apoptosis.

Conclusion

The results from the present study suggested that fluoxetine protects against big endothelin-1 induced anti-apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle cells, potentially by decreasing intracellular concentrations of Ca²⁺.     

Differential diagnosis of complex renal cysts based on lesion size along with the Bosniak renal cyst classification

Purpose

To identify size criteria for complex cystic renal masses that can distinguish renal cell carcinoma from benign cysts supplementing the Bosniak classification.

Materials and Methods

We reviewed the records of 97 patients who underwent surgery for complex cystic renal masses from January 2001 to April 2010. The pathological results were compared with the lesion sizes measured by preoperative computed tomography and other radiological features (contrast enhancement, irregularities of cyst walls and septa, and calcification) were also obtained for categorization according to the Bosniak renal cyst classification.

Results

Malignancy was significantly associated with cyst size (>2 cm), male gender, and younger patient age (<50 years). According to the Bosniak classification, there was no category I cyst, and all 8 category II cysts were benign. However, 3 of 18 (17%) category IIF cysts, 21 of 39 (54%) category III cysts, and 29 of 32 (90%) category IV cysts were malignant. All category IIF cysts were benign in patients older than 50 years of age.

Conclusion

Many complex cystic renal masses smaller than 2 cm were benign. We suggest that lesion size should be taken into account when formulating treatment plans for complex cystic renal masses.     

Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care

Background

It is estimated that one-quarter of adults in the UK drink at harmful/hazardous levels leading to increased mortality and alcohol liver disease (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in primary care the feasibility of alcohol misuse screening in adults, using the AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for ALD using newer non-invasive serum markers of fibrosis.

Aim

To explore patients’ experiences of taking part in ALDDeS and understanding of the delivery and process of screening for ALD using self-report questionnaires and feedback of liver fibrosis risk using levels of non-invasive serum markers.

Design and setting

A nested qualitative study based in five primary care practices in the UK.

Method

From a sample of patients who were identified as drinking at harmful/hazardous levels, 30 participants were identified by maximum variation sampling for qualitative in-depth interviews. Using the principles of constant comparison the transcribed interviews were thematically analysed.

Results

Receiving a postal AUDIT questionnaire was viewed as acceptable by participants. For some completing the AUDIT increased awareness of their hazardous alcohol use and a positive blood test indicating liver fibrosis was a catalyst for behaviour change. For others, a negative blood test result provided a licence to continue drinking at hazardous levels. A limited understanding of safe drinking and of ALD was common.

Conclusion

Educational and training needs of primary care professionals must be taken into account, so that patients with marker levels indicating low risk of fibrosis are correctly informed about the likely risks of continuing to drink at the same levels.     

Advanced fibrosis is not a negative pretreatment predictive factor for genotype 2 or 3 chronic hepatitis C patients

Background/Aims

Chronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C.

Methods

We retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed.

Results

Data from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage.

Conclusions

Compared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis.     

Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats

Study Objectives:

Because the maternal environment can affect several physiological functions of the newborn, the aim of the present study was to examine the impact of sleep restriction during pregnancy on renal morphology and function in young offspring.

Design:

Female 3-month-old Wistar rats were divided in 2 experimental groups: C (control) and SR (sleep restriction between the 14th and 20th day of pregnancy). Pregnancy was confirmed by vaginal smear. SR females were subjected to sleep restriction by the multiple platform technique for 20 h daily. After birth, only male litters (6 for each mother) were selected and designated OC (offspring from C) and OSR (offspring from SR). At 2 months of age, blood pressure (BP) was measured by tail plethysmography; at 3 months the renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular area, and number of glomeruli per mm³ were evaluated.

Measurements and Results:

Offspring from SR had higher systolic blood pressure than OC. In this group (OSR), we also observed significant increase in RPF and GFR, enlarged glomeruli diameter, and reduced number of glomeruli per mm³ of renal tissue.

Conclusions:

Our data suggest that sleep restriction during pregnancy is able to modify renal development, resulting in morphologic and functional alterations in young offspring.

Citation:

Thomal JT; Palma BD; Ponzio BF; Franco MCP; Zaladek-Gil F; Fortes ZB; Tufik S; Gomes GN. Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats. SLEEP 2010;33(10):1357-1362.     

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS)

Background

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals.

Aim

To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption.

Design and setting

A community feasibility study in nine general practice sites in Hampshire.

Method

Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis.

Results

In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives.

Conclusion

Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.     

The association between symptoms and bladder or renal tract cancer in primary care: a systematic review

Background

Appropriate selection for further investigation of patients presenting in primary care with symptoms that may indicate cancer is key to early diagnosis.

Aim

To quantify the risk of urinary tract cancer in patients presenting in primary care with symptoms that may indicate bladder or renal cancer.

Design and setting

Systematic review of studies relating to bladder or renal cancer in primary care.

Method

Databases searched were MEDLINE, PreMEDLINE, Embase, the Cochrane Library, Web of Science (SCI and SSCI), and ISI Proceedings from 1980 to August 2014, and PsycINFO (1980–2012) and BioMed Central (inception to 2012) for retrospective, prospective, or case-control diagnostic accuracy studies of symptomatic patients presenting to primary care with one or more symptoms for whom follow-up data were available. The target conditions were bladder or renal cancer. The studies were appraised using the QUADAS-2 tool.

Results

Eleven studies with 3 451 675 patients were included. The positive predictive value (PPV) from meta-analysis of visible haematuria was 5.1% in adult patients. It increased with age and was higher in males. The PPVs of other single symptoms were very low, with the highest non-haematuria PPV being 1.4% for anaemia in males. Fewer data were available on the PPVs of symptom combinations. Generally, these data showed that, with the exception of symptom combinations including haematuria, these were very low.

Conclusion

The only high-risk feature of bladder/renal cancer in primary care was visible haematuria, and this clearly warrants investigation. However, not all patients with one of these cancers experience haematuria, so a policy restricting investigation to patients with haematuria will inevitably delay the diagnosis in some patients.     

Rare Acute Kidney Injury Secondary to Hypothyroidism-Induced Rhabdomyolysis

Purpose

Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients.

Materials and Methods

We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism-induced rhabdomyolysis from January 2006 to December 2010.

Results

Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification.

Conclusion

Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.     

Normative ultrasound values of renal parenchymal thickness among adults in Enugu,South-East Nigeria

Background

Reduction in renal length was found to be an insufficient independent indicator of chronic renal disease.

Objective

To determine the ultrasound normative values of renal parenchymal thickness (RPT) among adults and correlate them with age and somatometric parameters.

Methods

This was a prospective clinic based study involving 310 normal adults (135 males and 175 females) scanned at University of Nigeria Teaching Hospital, Enugu between August 2003 and November 2004. The RPT measurements were made from the outer renal cortical margin to the outer margin of the sinus echoes at the three major poles. The age, height, weight and body mass index were recorded for each subject.

Results

The average RPT are 1.85 ± 0.20 cm for the right kidney and 1.95 ± 0.19 cm for the left kidney. RPT exhibited strong positive correlation with height, weight and body mass index and significant negative correlation with age. No significant difference in mean RPT of both kidneys between genders (p > 0.05). The mean RPT of the left kidney was found to be statistically higher than that of the right kidney (p < 0.05).

Conclusion

Normal values of RPT are important in the evaluation of patients with chronic renal disease.     

Prevalence of Microalbuminuria among secondary school children

Background

Microalbuminuria is an early sign of kidney and cardiovascular damage. Therefore, early detection in asymptomatic individuals may be helpful in preventing deterioration in renal function.

Methods

We carried out a cross-sectional study of 820 secondary school students aged 10 – 19 years from September to November 2008. The urine samples of 615 (75.0%) without overt proteinuria and haematuria were tested for microalbuminuria using the micral test strips. Values of greater than 20mg/L were considered positive.

Results

There were 299 (48.6%) males and 316 (51.4%) females, with a M:F ratio of 1:1.1. The prevalence of microalbuminuria as seen in 214 of the students was 33.2%. It was significantly higher in females (45.3%), obese subjects (35.4%), those with hypertension (70.6%), those with positive family history of hypertension (59.5%), and diabetes mellitus (46.4%). Microalbuminuria was found in 1 of the 2 subjects who had features of DM and in one subject with sickle cell anemia.

Conclusion

The prevalence of microalbuminuria in Nigerian adolescents is high. We recommend routine screening for microalbuminuria in adolescents for early detection and prevention of renal damage.     

Left Ventricle Fibrosis Associated With Nonsustained Ventricular Tachycardia in an Elite Athlete: Is Exercise Responsible? A Case Report

Objective:

To emphasize the potentially harmful effects of high-intensity exercise on cardiac health and the fine line between physiologic and pathologic adaptation to chronic exercise in the elite athlete. This case also highlights the crucial need for regular evaluation of symptoms that suggest cardiac abnormality in athletes.

Background:

Sudden cardiac death (SCD) of young athletes is always a tragedy because they epitomize health. However, chronic, high-intensity exercise sometimes has harmful effects on cardiac health, and pathologic changes, such as myocardial fibrosis, have been observed in endurance athletes. In this case, a highly trained 30-year-old cyclist reported brief palpitations followed by presyncope feeling while exercising. Immediate investigations revealed nonsustained ventricular tachycardia originating from the left ventricle on a stress test associated with myocardial fibrosis of the left ventricle as shown with magnetic resonance imaging. Despite complete cessation of exercise, life-threatening arrhythmia and fibrosis persisted, leading to complete restriction from competition.

Differential Diagnosis:

Hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, myocarditis, postmyocarditis, use of drugs and toxic agents, doping, and systemic disease.

Treatment:

The arrhythmia could not be treated with catheter ablation procedure or drug suppression. Therefore, the athlete was instructed to withdraw completely from sport participation and to have a medical follow-up twice each year.

Uniqueness:

To our knowledge, no other report of left ventricle exercise-induced fibrosis associated with life-threatening arrhythmia in a living young elite athlete exists. Only postmortem evidence supports such myocardial pathologic adaptation to exercise.

Conclusions:

To prevent SCD in young athletes, careful attention must be paid to exercise-related symptoms that suggest a cardiac abnormality because they more often are linked to life-threatening cardiovascular disease.     

Symptoms and risk factors to identify women with suspected cancer in primary care: derivation and validation of an algorithm

Background

Early diagnosis of cancer could improve survival so better tools are needed.

Aim

To derive an algorithm to estimate absolute risks of different types of cancer in women incorporating multiple symptoms and risk factors.

Design and setting

Cohort study using data from 452 UK QResearch® general practices for development and 224 for validation.

Method

Included patients were females aged 25–89 years. The primary outcome was incident diagnosis of cancer over the next 2 years (lung, colorectal, gastro-oesophageal, pancreatic, ovarian, renal tract, breast, blood, uterine, cervix, other). Factors examined were: ‘red flag’ symptoms including weight loss, abdominal pain, indigestion, dysphagia, abnormal bleeding, lumps; general symptoms including tiredness, constipation; and risk factors including age, family history, smoking, alcohol intake, deprivation, body mass index (BMI), and medical conditions. Multinomial logistic regression was used to develop a risk equation to predict cancer type. Performance was tested on a separate validation cohort.

Results

There were 23 216 cancers from 1 240 864 females in the derivation cohort. The final model included risk factors (age, BMI, chronic pancreatitis, chronic obstructive pulmonary disease, diabetes, family history, alcohol, smoking, deprivation); 23 symptoms, anaemia and venous thrombo-embolism. The model was well calibrated with good discrimination. The receiver operating curve statistics were lung (0.91), colorectal (0.89), gastro-oesophageal (0.90), pancreas (0.87), ovary (0.84), renal (0.90), breast (0.88), blood (0.79), uterus (0.91), cervix (0.73), other cancer (0.82). The 10% of females with the highest risks contained 54% of all cancers diagnosed over 2 years.

Conclusion

The algorithm has good discrimination and could be used to identify those at highest risk of cancer to facilitate more timely referral and investigation.     

Association between cystic fibrosis transmembrane conductance regulator gene mutations and susceptibility for childhood asthma in Korea

Purpose

Classic cystic fibrosis is now known part of cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders. These include a wide spectrum, from multi-system disorders, such as cystic fibrosis, to mono-symptomatic conditions, such as chronic pancreatitis or congenital bilateral absence of the vas deferens. However, respiratory disease is considered typical for the multi system disorder, cystic fibrosis, and is the major cause of morbidity and mortality. The purpose of this study was to evaluate the potential effects of CFTR gene mutations in Korean children with asthma.

Materials and Methods

We selected 14 mutations identified in Korea and each of the 48 children with and without asthma were genotyped for the case-control study.

Results

No significant differences were found in genotype and allele frequencies of the 9 polymorphisms observed between the non-asthma and asthma groups. In a haplotype determination based on a Bayesian algorithm, 8 haplotypes were assembled in the 98 individuals tested. However, we also did not find any significant differences in haplotype frequencies between the non-asthma and asthma groups.

Conclusion

We have concluded that this study did not show any evidence in support of providing that CFTR genetic variations significantly contribute to the susceptibility of asthma in Korean children.