Hyperventilation response in the electroencephalogram and psychiatric problems in children with primary monosymptomatic nocturnal enuresis

OBJECTIVES: The aim of this study was to determine the frequency of an increased hyperventilation (HV) response in the electroencephalogram and to compare the results of psychometric assessments and electroencephalography (EEG) patterns in children with and without primary monosymptomatic nocturnal enuresis and in dry siblings of enuretics. We also compared the results of psychometric assessments and EEG patterns between enuretic and non-enuretic children. MATERIAL AND METHODS: The study included 89 children divided into three groups: 41 with primary monosymptomatic nocturnal enuresis, their 29 dry siblings and 19 with no history of voiding dysfunction (controls). Resting EEG changes were evaluated in all children. In addition to a psychiatric evaluation, the Maudsley Obsessive Compulsive Questionnaire, the Beck Child Depression Inventory and the State and Trait Anxiety Inventory for Children were used to assess obsessive-compulsive disorder, depression and anxiety, respectively. RESULTS: The time at which real words were first spoken occurred significantly later in enuretic children (p<0.01). The frequency of EEG abnormalities was significantly higher in the enuresis group and in their dry siblings than in the control group (p<0.01). Additionally, as an indicator of cortical dysmaturity, an increased HV response was observed more often in enuretic children and their dry siblings than in the control group (p<0.001). Anxiety scores for the enuretic children were higher than those for the controls (p<0.01). There was no significant difference in psychiatric problems between the enuresis and control groups (p>0.05). CONCLUSIONS: The increased frequency of a high-level HV response in resting-state EEG recordings and the anxiety scores suggested that delayed cortical maturity and high anxiety may be important factors in the pathogenesis of primary monosymptomatic nocturnal enuresis. The HV responses in the dry siblings of the enuretic children may emphasize the relationship between insufficient cerebral maturation and the genetic origin of nocturnal enuresis.     

The impact of monosymptomatic nocturnal enuresis on attachment parameters

OBJECTIVE: This study assesses the impact of monosymptomatic nocturnal enuresis (MSNE) on the child's perception of quality of attachment to a caregiver and the caregiver's perception of dissociative behavior. MATERIAL AND METHODS: The study group comprised 47 boys and 63 girls (mean age 11.7 years; range 9-18 years). Subjects were classified into two groups as follows: Group I (normal children without nocturnal enuresis); or Group II (children with MSNE). MSNE was defined as more than three wet episodes per week without day-time enuresis, urge incontinence, frequency or dysuria. The Adolescent Attachment Questionnaire (AAQ) was administered to the children and the Child Dissociative Checklist (CDC) to the caregiver. Comparison groups were divided by gender, feeding method and type of caregiver. The AAQ and CDC scores in each subgroup were compared between the enuretic and non-enuretic groups. RESULTS: Mean scores for attachment pathology were significantly higher in the enuretic (n = 50) than the non-enuretic group (n = 60) (p < 0.05). The most significant attachment pathology was evident for the AAQ Angry Distress dimension in the nocturnally enuretic group. Caregivers' CDC scores did not differ significantly between the two groups. Highest mean dissociation scores were evident for those children whose caregiver was not a biologic parent or grandparent. CONCLUSIONS: MSNE may negatively impact the child's perception of the quality of attachment. Caregivers reported no significant dissociative behavior in nocturnally enuretic children. With prolonged nocturnal enuresis, physicians should be aware of the possibility of anger and distress within the child-caregiver relationship. In such cases, the modified treatment protocol should include psychologic counseling and support.     

Influence of uridine diphosphate-glucuronosyltransferases (1A9) polymorphisms on mycophenolic acid pharmacokinetics in patients with renal transplant

Background: There are differences in pharmacokinetic of mycophenolic acid among individuals. The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MPA. The aim of this study was to explain MPA pharmacokinetics in UGT1A9 1399 C?>?T polymorphisms in Turkish renal transplant patients.

Patients and methods: One hundred and twenty-five living-donor transplant recipients and 100 healthy control subjects underwent UGT1A9 1399 C?>?T genotyping using polymerase chain reaction–restriction fragment length polymorphism. Concentrations of MPA were determined with Cloned Enzyme Donor Immunoassay (CEDIA). Besides that, all the patients were monitored for acute rejection and graft function during the study period.

Results: The UGT1A9 1399 C?>?T CC, CT, and TT genotype frequencies among patients were, respectively, 68.0%, 23.2%, and 8.8%. The CC, CT, and TT genotype frequencies among controls were, respectively, 63.0%, 23.0%, and 14.0%. There was no significant difference between patients and controls (p?=?.480, p?=?.999, p?=?.286, respectively). At first month, respectively, through blood concentrations of MPA were significantly higher in UGT1A9 1399 C?>?T TT carriers than in CT and CC carriers (p?=?.046). The doses for these patients were lower at first month (p?=?.021). Acute rejection episodes were not associated with the CC vs CT or TT genotypes (p?=?.064).

Conclusions: Our results demonstrated a correlation between the UGT1A9 1399 C?>?T polymorphism and MPA pharmacokinetics among renal transplant patients. Determination of UGT1A9 polymorphism may help to achieve target of MPA blood concentrations.     

Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study

OBJECTIVE: To evaluate any differences in the characteristics of primary nocturnal enuresis (PNE) between younger enuretic children and adolescents. SUBJECTS AND METHODS: In all, 21 000 questionnaires designed to determine the presence or absence of bed-wetting, diurnal incontinence, frequency of wetting, systemic illness, and family history, were sent to children aged 5-19 years from 67 kindergartens, primary schools and secondary schools randomly selected by a computer from different areas in Hong Kong. In addition, questions were asked to evaluate when and how the parents became aware that bed-wetting is a significant medical problem deserving attention in children after the age of 5 years. RESULTS: Of the 21,000 questionnaires distributed, 16 512 (78.6%) were completed. Among the respondents, 512 children (302 boys, 210 girls) had PNE; of these, 106 (20.7%) also had daytime incontinence. There was a marked reduction in the overall prevalence of PNE with advancing age. At 5 years old, 16.1% of children had PNE (20.7% boys, 10.8% girls; at age 9 and 19 years, 3.14% and 2.2% of children had PNE, respectively. However, this reduction was significantly more apparent among those with mild enuretic symptoms (wet <3 nights/week) than in those with more frequent bed-wetting. Furthermore, younger enuretic children behaved very differently from adolescents and older patients. As age increased there was a significant tendency towards more severe enuretic symptoms. At age 5 years, 14.3% of enuretic children wet 7 nights/week, compared with 48.3% at age 19 years (P < 0.001). In addition, significantly more adolescent boys aged >10 years had daytime urinary incontinence than had enuretic children aged < or = 10 years (32% vs 14.6%, respectively, P < 0.001). Most (89%) parents only became aware that bed-wetting was a significant medical problem deserving attention through material in the mass media over the past 3-4 years. CONCLUSIONS: The present finding suggesting that PNE spontaneously resolves with increasing age probably applies only to those with mild enuretic symptoms. There are significant differences in characteristics between younger enuretic children and older subjects. As age increases there is an increasing proportion of enuretic patients with more severe bed-wetting. Enuretic children aged >10 years and adolescents have significantly more daytime urinary symptoms and incontinence. The previously reported low prevalence of PNE in Hong Kong was probably due to parental indifference to the problem.     

Association of the T-786C, G894T and 4a/4b polymorphisms of the endothelial nitric oxide synthase gene with vasculogenic erectile dysfunction in Iranian subjects

What's known on the subject? and What does the study add? We know that nitric oxide (NO) plays a significant role in penile tumescence. NO is produced during enzymatic conversion of L‐arginine to L‐citrulline by three distinct isoforms of NO synthase (NOS), namely, inducible (iNOS), endothelial (eNOS) and neural (nNOS). The endothelial isoform of NOS (eNOS), encoded by the NOS3 gene, is the main source of NO. We determined all three eNOS gene polymorphisms in men with vasculogenic erectile dysfunction. There was a significant difference between the group of men with vasculogenic erectile dysfunction and normal healthy men when compared by genotype distribution.

OBJECTIVE

? To investigate the association of the T‐786C, G894T and variable number of tandem repeats (VNTRs) in intron 4 (a/b) polymorphisms of the eNOS gene in Iranian subjects with vasculogenic erectile dysfunction (ED).

PATIENTS AND METHODS

? A total of 322 consecutive patients with vasculogenic ED were recruited. Patients with concomitant risk factors for ED were excluded. ? Patients with ED were identified based on history‐taking, detailed physical examination, serum biochemistry, sex hormone measurements, application of the International Index of Erectile Function (IIEF) questionnaire, and penile duplex Doppler ultrasonography after intracavernosal injection of 20 µg prostaglandin E₁. The control group comprised 318 age‐matched healthy male volunteers. ? Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism and the T‐786C, G894T and VNTR intron 4 polymorphisms of the eNOS gene were determined.

RESULTS

? After multivariate regression analysis, significant differences were seen in the frequencies of genotypes and alleles of the two T‐786C and G894T polymorphisms when patients with ED and normal controls were compared. ? In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the ‐786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28–4.25; P= 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53–4.87; P= 0.001). ? The data showed a higher prevalence of the T‐786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88–3.65; P= 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24–2.83; P= 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42–4.26; P= 0.001) in patients with ED than in the controls.

CONCLUSIONS

? The findings of the present study suggest that the eNOS T‐786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease. ? Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED.     

Adrenomedullin and nitrite levels in children with primary nocturnal enuresis

Primary nocturnal enuresis (PNE) is the most common type of nocturnal enuresis in children, but its etiology remains unclear. Recent studies indicated the differences in urinary electrolytes in enuretic children, and stressed the existence of a renal tubular maturation defect. In this study, 30 children (aged 6-12 years) with PNE were investigated in comparison with 18 healthy controls. We evaluated plasma antidiuretic hormone, electrolytes, 24-h urine volume, osmolarity, and urinary electrolytes. Unlike other studies, we firstly assessed the plasma and urinary adrenomedullin (AM) and total nitrite levels, a stable product of nitric oxide (NO), and investigated their relationship with urinary electrolytes. The plasma AM and total nitrite levels were significantly lower than controls. Urine volume (24-h) and potassium excretion were higher than in controls. However, 24-h urinary osmolarity and excretion of AM were significantly lower than in controls. Our results indicate that there may be a problem in renal regulation of potassium in children with PNE. Although decreased levels of AM and total nitrite may be a compensatory response to abnormal potassium and water excretion, further investigations are required to exclude whether the renal synthesis of AM and NO are also deficient in these children.     

Abnormal circadian blood pressure regulation in children with nocturnal enuresis

Introduction: To investigate autonomic nervous system function in enuretic children by performing ambulatory blood pressure monitor (ABPM) for 24?h. Methods: Twenty-eight children ranging in age from 6 to 15 years with primary nocturnal enuresis and 27 age-matched healthy controls were enrolled and they get 24?h ABPM. Hypertension was defined as standard deviation score (SDS)?>?1.64 (i.e., >95th percentile) adjusted for gender and height. Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were carried out in all children. They have also requested to have a diary about daily fluid intake and urine volume. Results: Although the mean 24-h and daytime diastolic blood pressure (BP) did not differ between the groups, systolic BP (SBP) was significantly higher in enuretic children (p?<?0.05). The mean night-time SBP, DBP values, SDS and BP loads were found to be significantly higher than those in the controls (p?<?0.01). A lack of nocturnal decrease was more prevalent in the enuretic children compared with the control subjects, the difference was statistically significant for DBP but not for SBP. Patients with elevated night-time BP load was found to have higher frequency of urinary incontinence per week as well as per night when compared with enuretic children with normal night-time BP load (r?=?0.72, r?=?0.69, p?<?0.01, respectively). Conclusion: Subtle abnormalities of circadian BP regulation in enuretic children indicated by a selective elevation of nocturnal SBP, DBP, and MAP, and attenuated nocturnal dipping may reflect sympathetic hyper activation and its possible role in pathogenesis of enuresis.     

Association of endothelial nitric oxide synthase gene polymorphisms with end-stage renal disease: a systematic review and meta-analysis

Background and objective: Endothelial nitric oxide synthase (eNOS) is one of the potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be involved in the progression of renal disease, and may be the causative factors that contribute to the deterioration of renal functions. During the past decades, several studies investigated the association of eNOS polymorphisms with the risk of end-stage renal disease (ESRD), but the results remain unclear and the mechanisms are not defined. Our study was designed to examine the role of different eNOS genetic polymorphisms in the progression of ESRD. Materials and methods: Relevant studies were identified through PubMed, Embase, Medline and CNKI (China National Knowledge Infrastructure) database published between January 2000 and November 2013. The association between eNOS polymorphisms and ESRD susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models. Results: Sixteen articles were identified for the analysis of association between eNOS gene polymorphisms and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients and 1171 controls for G894T, and 513 patients and 487 controls for T786C were included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a significant association in the global population (OR?=?1.47, 95% CI?=?1.05–2.06, p?=?0.03) in a random-effect model; T allele of G894T was also significantly associated with ESRD susceptibility in overall populations (OR?=?2.12, 95% CI?=?1.44–3.12, p?=?0.0001). Furthermore, 4a and T carriers were significantly associated with ESRD risk as well. No association was found between T786C polymorphism and ESRD. Conclusion: The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with ESRD susceptibility, indicating that 4a and T allele carriers might become significant genetic molecular markers for the onset of ESRD in overall populations. However, more studies should be performed in the further studies.     

TGF-β1 gene polymorphisms and primary vesicoureteral reflux in childhood

The aim of this study was to assess the association between the transforming growth factor-β1 (TGF-β1) gene polymorphisms rs1800469 (commonly known as T-509C) and rs1982073 (commonly known as Leu ¹⁰→Pro) and primary vesicoureteral reflux (VUR) and renal scarring. Using a case–control approach, we examined 121 children with primary VUR and 169 controls. Genotyping of the TGF-β1 gene polymorphisms was performed by restriction fragment length polymorphism (RFLP) analysis. The ^99mTc-DMSA– or ^99mTc-unitiol–single photon emission computed tomography method was used to evaluate renal scars in 84 of 121 VUR children. Statistical analysis revealed differences in rs1800469 genotype frequencies between VUR patients and controls (p = 0.0021). Our data demonstrate that individuals homozygous for the TT genotype are at risk of primary VUR [odds ratio (95% confidence interval) = 2.7 (1.46–5.08)]. Distribution of the rs1982073 polymorphism was similar in VUR children and controls. In terms of renal scarring, patients were stratified into non-scar and scar subgroups, and no differences in the genotype frequencies of either polymorphism was found. Previous reports have shown that the TT genotype of the rs1800469 polymorphism is a risk factor for renal scarring in primary VUR, and the results of our study suggest that this same polymorphism is associated with susceptibility to this congenital uropathy.     

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD

Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine. The rare genotype (TT) of the C677T polymorphism has previously been demonstrated to be associated with increased plasma homocysteine levels in individuals with inadequate plasma folate levels. Recently, the TT genotype has been found to be associated with reduced bone mass. We therefore examined if the C677T polymorphism in the MTHFR gene is associated with changes in bone mass and risk of osteoporotic fractures in 388 osteoporotic patients and 336 normal individuals. The distributions of the genotypes CC, CT and TT in women with osteoporotic vertebral fractures and normal controls were 43.5%, 42.2% and 14.3% and 52.0%, 42.0% and 8.0%, respectively, ²=5.62, P=0.06. Since studies of the functionality of this polymorphism have revealed that only the TT genotype is associated with biochemical changes, we also compared the prevalence of the TT genotype versus the CT- and CC genotypes in patients and controls and found that the TT genotype is significantly more common in women with vertebral fractures (14.3%) compared with normal controls (8.0%), ²=4.31, P<0.05. Logistic regression analysis demonstrated that vertebral fractures were significantly associated with BMD (lumbar spine) and height but only marginally with the MTHFR genotype (P=0.06). Multiple linear regression analysis revealed that weight, age and the MTHFR polymorphism were predictors of lumbar spine BMD in women. However, age- and gender-corrected BMD of the lumbar spine and the hip was not significantly different between MTHFR genotypes. Furthermore, individuals with the TT genotype did not have BMD significantly lower than the combined group of individuals with the CT- or CC genotypes. In conclusion, we have demonstrated that the rare TT genotype of the C677T polymorphism in the MTHFR gene is associated with increased risk of osteoporotic fractures in women and a weak predictor of lumbar spine BMD.     

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Summary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fractures. Methods We studied 498 women with hip fractures and 356 controls. A C/G polymorphism of the aromatase gene and a T/C polymorphism of the estrogen receptor α gene were analyzed using Taqman assays. Aromatase gene expression was determined in 43 femoral neck samples by real-time RT-PCR. Results There were no significant differences in the overall distribution of genotypes between the fracture and control groups. However, among women with a TT genotype of the estrogen receptor, the CC aromatase genotype was more frequent in women with fractures than in controls (39 vs. 23%, p = 0.009). Thus, women homozygous for T alleles of estrogen receptor and C alleles of aromatase were at increased risk of fracture (odds ratio 2.0; 95% confidence interval 1.2–3.4). The aromatase polymorphism was associated with RNA levels in bone tissue, which were three times lower in samples with a CC genotype (p = 0.009). Conclusions These common polymorphisms of the aromatase and estrogen receptor genes appear to interact, influencing the risk of hip fractures in women. Supported by grants from Fondo de Investigaciones Sanitarias (FIS 04/28 and 06/34).     

Pupillometric assessment of autonomic nervous system in children with functional enuresis

Functional enuresis is defined as repeated voiding of urine into bed or clothes in children after 5 years of age following the exclusion of major somatic diseases. Autonomic nervous system dysregulation has been proposed as a pathophysiologic mechanism in the etiopathogenesis. The objective of this study was to evaluate autonomic nervous system functions with pupil diameter measurement in enuretic children. The study group consisted of 17 children with functional enuresis (ten boys, seven girls), and the control group consisted of 34 healthy children (20 boys, 14 girls). Pupil diameter measurements were performed under photopic and mesopic lighting conditions by using a pupillometer. Mean photopic pupil diameter was found to be larger in the enuretic children than in the healthy controls (4.47 ± 0.52 mm vs. 4.03 ± 0.75 mm; P = 0.03). Autonomic nervous system imbalance of the ocular system is considered to be part of the autonomic nervous system dysregulation in functional enuretic children.     

IL‐16 polymorphism and risk of renal cell carcinoma: Association in a Chinese population

Objectives: Interleukin‐16 (IL‐16) plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. A T‐to‐C polymorphism at the ‐295 position in the promoter region of the IL‐16 gene has been described. This variation might lead to altered IL‐16 expression, and might modulate an individual's susceptibility to cancer. The objective of the present study was to determine if IL‐16 polymorphism is associated with risk of renal cell carcinoma (RCC). Methods: A case–control study including 335 RCC cases and 340 cancer‐free controls was carried out. All subjects were genetically unrelated ethnic Han Chinese recruited from a single institution between July 2006 and July 2009. The IL‐16 ‐295 T>C polymorphism was determined by using the polymerase chain reaction‐restriction fragment length polymorphism method. Serum samples were available for 70 RCC cases and 96 controls to detect IL‐16 concentration. Results: Compared with the IL‐16 ‐295 TT genotype, the CC genotype had a significantly decreased RCC risk (adjusted odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.18–0.66). Furthermore, a significant decreased risk of RCC was found in the combined variant genotypes CT + CC compared with the TT genotype (adjusted OR = 0.68, 95% CI = 0.50–0.93). In addition, the serum IL‐16 levels in RCC patients were significantly lower than those in controls (P < 0.001). Furthermore, patients carrying CC genotype or CT genotype had higher serum IL‐16 levels than TT carriers. Conclusion: IL‐16 ‐295 T>C polymorphism is significantly associated with a higher risk of developing RCC in Chinese population.     

冠心病与内皮型一氧化氮合酶基因多态性的关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因-786T/C,4a4b,894G/T等3个多态性位点与冠心病(CAD)发病相关.方法 对146例中国汉族人群CAD患者和113例正常对照进行遗传学分析,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR技术分析2个SNP位点即-786T/C和894G/T,以及1个VNTR位点4a4b,检测各位点基因型和等位基因频率,采用HaploView 4.0及SPSS 13.0软件经x2检验比较两组间各位点基因型及等位基因频率的差异.结果 CAD组中eNOS基因-786T/C位点CC基因型频率为2.0%,4a4b位点4a/4a基因型频率为5.4%,对照组eNOS基因-786T/C位点CC基因型频率为0.0%,4a4b位点4a/4a基因型频率为0.9%,差异有统计学意义(P＜0.05).CAD组和对照组在eNOS基因的894G/T位点等位基因和基因型频率分布差异均无统计学意义(P＞0.05).结论 eNOS基因-786T/C和4a4b多态性与中国汉族人群CAD存在关联,C等位基因和4a等位基因可能是CAD发病的危险因素.eNOS基因894G/T位点与CAD发病无明显相关.

Abstract：

Objective To investigate the relationship between the 3 polymorphisms ( -786T/C,4a4b,894G/T) in endothelial nitric oxide synthase (eNOS) gene and coronary artery disease (CAD).Methods 146 patients with CAD and 113 healthy unrelated individuals in a Chinese Han nation were involved.The genotype and allele frequency of each polymorphism of the eNOS gene in these patients and normal controls were examined by using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or PCR methods.Genotypes and allele frequency were analyzed by HaploView 4.0 and SPSS13.0 software.Results The frequency of CC genotype of the -786T/C was 2.0%,and that of 4a/4a genotype of the 4a4b was 5.4% in CAD.The frequency of CC genotype of the - 786T/C was 0.0%,and that of 4a/4a genotype of the 4a4b was 0.9% in controls ( P＜0.05 ).There were significant differences in both allele and genotype frequency of -786T/C and 4a4b between CDA group and control group.Between patients with CAD and controls,there were no significant differences in the frequency of the genotypes and alleles of the 894G/T in eNOS gene.Conclusion The - 786T/C and 4a4b polymorphisms of eNOS gene may be associated with CAD.The individuals with C allele of - 786T/C and 4a allele of 4a4b are susceptible to CAD.There is no significant correlation between 894G/T polymorphism in eNOS gene and CAD.     

Association between ABCB1 (MDR1) Gene 3435 C>T Polymorphism and Colchicine Unresponsiveness of FMF Patients

The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.     

Effects of the T-786C,G894T,and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89–7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78–4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64?8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b “a” variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68–3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21–6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the “a” allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74–8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64–8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33–0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26–0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.     

An epidemiological study of nocturnal enuresis in Taiwanese children

OBJECTIVE: To estimate the prevalence of primary nocturnal enuresis (PNE) in Taiwanese children, and to examine factors associated with PNE and its severity. SUBJECTS AND METHODS: In all, 1683 questionnaires were sent to parents of schoolchildren aged 6-11 years randomly selected from three primary schools in Taipei City, Taiwan. The questionnaire was designed to collect information about the prevalence of and factors associated with PNE. RESULTS: Of the questionnaires distributed, 1176 (70%) were completed. PNE was reported in 92 (8%) of the children; nine (10%) of these children were wet > 3 nights per week. Factors associated with PNE included male gender, deep sleep, divorced parents or separated family and a positive family history of enuresis. Of these factors, only those children with deep sleep were more likely to have > 3 wet nights per week. CONCLUSION: The prevalence of and factors associated with PNE in Taiwan are similar to those reported in Western countries, but the percentage of children with severe enuresis is lower than in Sweden, France and Turkey. Deep sleepers are more likely to have severe enuresis.     

Association between transforming growth factor-β1gene-509C/T polymorphism and susceptibility of IgA nephropathy: a meta-analysis

A role for transforming growth factor-β₁gene has been suggested in the etiology of IgA nephropathy. However, results have been inconsistent. In this study, a meta-analysis was performed to further clarify the association between transforming growth factor-β₁-509C/T gene polymorphism and the susceptibility of IgA nephropathy. PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals were calculated using a fixed-effects model or random-effects model. A total of eight publications involving 1355 IgA nephropathy patients and 1464 controls met the inclusion and were analyzed. The pooled ORs for the association between TGF-β₁gene-509C/T polymorphism and IgA nephropathy risk were not statistically significant under all genetic models (for CT+TT vs. CC: OR?=?1.09; 95% CI?=?0.92–1.29, p?=?0.490; for TT vs. CT+CC: OR?=?1.14; 95% CI?=?0.94–1.38, p?=?0.081; for CC vs. TT: OR?=?0.87; 95% CI?=?0.69–1.08, p?=?0.195; for C allele vs. T allele: OR?=?0.92; 95% CI?=?0.83–1.03, p?=?0.149). In the stratified analysis by ethnicity, results also showed no significant association between TGF-β₁ gene-509C/T polymorphism and IgA nephropathy risk in both European and Asian populations. This meta-analysis does not support the hypothesis that TGF-β₁ gene-509C/T polymorphism is a risk factor for the development of IgA nephropathy.     

An epidemiological study of primary nocturnal enuresis in Chinese children and adolescents

AIMS: Assessment of the prevalence of primary nocturnal enuresis (PNE) and its risk factors in Chinese children and adolescents in the central areas of mainland China. METHODS: A cross-sectional study of PNE was performed by distributing 11799 self-administered questionnaires to parents of 5-18-year-old students in 32 schools of Henan province China. The questionnaire asked about sociodemographic data, PNE data, physical or psychological disorders, and family stressors. The PNE children were divided into a pediatric group (age 5-12) and an adolescent group (age 13-18). RESULTS: The response rate was 88% (10383/11799) in which 10088 (85.5%) were qualified to enter the final statistical analysis. The overall prevalence of PNE was 4.07% (95%CI 3.68-4.46) and that of marked PNE was 1.46% (95%CI 1.23-1.69). PNE was significantly more in boys than in girls. The prevalence decreased with age without gender bias. Of all enuretic children, 21.17% had daytime urinary symptoms and 22.87% had a positive family history. Only 6.08% of PNE had sought professional help. The episodic severity of PNE, associated daytime symptoms, positive family history, and seeking for professional help in adolescent group were significantly higher than those of pediatric group. Age, inhabitation (living in rural or urban areas), arousal dysfunction, associated daytime symptoms and family history were found to be significant predictors of marked PNE. Among PNE cases with a positive family history, there was no significant difference in the familial distribution between boys and girls. CONCLUSIONS: The prevalence of age-related PNE from Chinese school children is lower than those reported from western countries and other Asian countries. Age, inhabitation (rural or urban), arousal dysfunction, associated daytime symptom and family history are significant as predictors of marked PNE. The misconceptions among Chinese parents require health education intervention.