Association between cord blood IgE and genetic polymorphisms of interleukin-4, the β-subunit of the high-affinity receptor for IgE, lymphotoxin-α, and tumor Necrosis factor-α

High cord blood immunoglobulin E (cbIgE) is known to be associated with increased risks of atopic diseases in childhood. The relationship between genetic polymorphisms and high cbIgE has not been well documented. A cross-sectional study was conducted to assess the association between cbIgE and genetic polymorphisms of interleukin (IL)-4 -590C/T, the beta-subunit of the high-affinity receptor for IgE (FcepsilonRI-beta) E237G, lymphotoxin (LT)-alphaNcoI alleles, and tumor necrosis factor (TNF)-alpha -308G/A. A total of 320 mother-neonate pairs were recruited from four maternity hospitals from different locations of Taiwan. Cord blood was obtained and assayed for cbIgE. Polymerase chain reaction followed by restriction fragment length polymorphism was used to assess the genotypes. Three hundred pairs of mothers and neonates were included in the final analysis. Infants with IL-4 -590 C allele were found to have higher risk of elevated cbIgE (> or =0.35 IU/ml, 24.3%) (p = 0.004). After adjusting for gender, birth order, maternal age, and history of allergic disease in maternal and paternal families, odds ratios for CC and CT genotypes were 4.41 and 3.16 (95% confidence interval 0.78-22.67, and 1.66-6.13), respectively, using TT genotype as reference. The genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha were not associated with cbIgE before or after the adjustment. Our finding suggested a significant association of cbIgE with genetic polymorphism of IL-4 -590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha.     

基于Internet的遗传疾病登记、随访系统的设计与实现

本系统通过以Internet网为平台,将传统的医院/患者(咨询者)的遗传随访模式转为医院/Internet网/患者(咨询者)的新医疗模式,该系统会大大提高遗传随访的及时性和便利性;同时,会有利于遗传登记的开展,也有利于随访资料的保存。     

Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease

OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD.     

Exhaled nitric oxide and its long‐term variation in healthy non‐smoking subjects

Exhaled nitric oxide (NOexp) is an indicator of inflammation in the airways. Reference values obtained from healthy adults or information on long‐term variation of NOexp are not yet available. The aims of this pilot study were to collect values of NOexp from a selected group of healthy adults and to assess their long‐term variation. We studied 26 healthy subjects (age 21–48, 16 male, 10 female) with normal findings in flow‐volume spirometry, pulmonary diffusing capacity, relative amount of blood eosinophils, chest X‐ray and ECG at rest. NOexp was determined according to the European Respiratory Society guidelines during slow expiration against an airflow resistance. The measurements were repeated after 7 (n=13) and 23 days (n=17). The mean value of NOexp (n=26) was 6·9 ng g^–1 (95% confidence interval, 6·0–7·9 ng g^–1). The upper limit of intra‐individual variation (+2 SD) was 11·9 ng g^–1 and the lower limit (–2 SD) 1·9 ng g^–1, respectively. The mean (SD) value of NO production (NO output) was 39·1 pmol s^–1 (20 pmol s^–1). We found no correlation between NOexp and age (r=–0·06, P=0·78) and no association of NOexp with the gender (male vs. female, P=0·40). The intraindividual coefficient of variation (CoV) was 15·8% of NOexp and 20·7% of NO output within the interval of 7 days. CoV was 16·8% of NOexp and 18% of NO output within the interval 23 days. The results suggest that NOexp values over 12 ng g^–1 are abnormally high in healthy subjects. According to the results the change of NOexp by 30–35% or more within the interval of 1–3 weeks would be abnormal.     

Tests of autonomic dysfunction in patients with multiple sclerosis

Autonomic dysfunction is frequent in patients with multiple sclerosis (MS). The sympathetic skin response (SSR) and the R-R interval variation (RRIV) are simple electrophysiologic tests for the assessment of central and peripheral autonomic disturbances. Both tests were performed in 60 patients with clinically definite MS and 30 controls. The SSR was recorded simultaneously from both upper and both lower limbs. In all volunteers normal responses were recorded from the four limbs, but 39 patients (65%) showed abnormal responses in at least one limb. The reduction in amplitude of the response was correlated with patients' EDSS. In individual limbs, the SSR amplitude correlated with weakness, spasticity and cerebellar dysfunction, but was not sufficiently related to the deep sensory loss. The RRIV was abnormal in 48 MS patients (80%), as compared to the controls, but showed no significant relationship either to the EDSS or to the SSR. The sensitivity of SSR and RRIV is high and comparable with that of visual and somatosensory evoked potentials.     

Genetics: Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome

Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested.     

Neurology of the neuronal ceroid-lipofuscinoses: Late infantile and juvenile types

My experience with more than 80 cases of the late infantile and juvenile forms of the neuronal ceroid-lipofuscinoses over the last 5 years has led to the following realizations. The 2 variants are neurologically distinct entities and probably are the result of different genetic defects. Treatment includes supportive measures and anticonvulsant medication. Therapy for behavioral and psychiatric disturbances in the juvenile type proves to be particularly challenging as neuroleptic medications tend to worsen parkinsonian like symptoms. Neuropathologic and neuro radiologic explanation of clinical symptomatology correlates best with neuronal loss and not neuronal storage. There is a paucity of neuropathologic documentation of these 2 types; additional reports are encouraged.     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.     

Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.     

The Lewis blood group--a new genetic marker of ischaemic heart disease.

In a cohort of 3383 men aged 53 to 74 in the Copenhagen Male Study we investigated the association between ischaemic heart disease (IHD) and the Lewis blood group, assigned to chromosome 19. Among men with the Le(a-b-) phenotype, 8% had a history of non-fatal myocardial infarction, among others the frequency was 4%. The corresponding odds ratio was (95% confidence interval: CI) 1.9 (1.2-3.0) P < 0.01, men with Le(a-b-) had a risk-factor profile and pattern of disease resembling that of Reaven's syndrome X. In a subsequent prospective study 343 men with arteriosclerotic stigmas were excluded. The men had their morbidity and mortality recorded over the next 4 years. One-hundred-and-one men suffered IHD; 26 dying from IHD. In total 162 men died. Men with Le(a-b-) had an increased risk of death from IHD compared with others. Adjusted for age, relative risk (RR) (95% CI) was: 4.4 (1.9-10.3), P < 0.001, and for all causes of mortality: RR = 1.6 (1.0-2.6), P < 0.05. Men with the Le(a-b-) phenotype had an increased risk of an IHD event compared to men with other phenotypes (RR = 1.6 (0.9-2.8), P = 0.10) and a significantly higher IHD case fatality rate (RR = 2.8 (1.5-5.2), P = 0.01). The finding that the Le(a-b-) phenotype is a genetic marker of IHD risk may have implications in terms of prevention. The Le(a-b-) phenotype may also contribute to providing an explanation for the substantial ethnic differences found in the incidence of IHD. The similar risk-factor profile and pattern of disease found between Le(a-b-) men and individuals with Reaven's syndrome X is hypothesized to be due to a close genetic relationship on chromosome 19.