Gaucher disease type I, the non-neuropathic type, usually presents in adulthood with hepatosplenomegaly. We report here an adult with type I Gaucher disease presented with unusual and severe clinical ...manifestations.
Hepatosplenomegaly, bone crisis and fractures occurred at early childhood, and splenectomy was performed at the age of 5. Exophthalmos with increase in retrobulbar space was noted when the patient was 30. Cerezyme infusion started at the age of 32; but unfortunately, pulmonary arteriovenous malformation with dyspnea and hypoxemia was found two years later. Gene analysis revealed V375L/L444P mutations in the beta-glucocerebrosidase gene.
Although both eye and lung diseases have been associated with Gaucher disease, this is the first reported demonstration of exophthalmos and pulmonary arteriovenous malformation in the same patient. This case may therefore present an extremely severe and unusual form of type I Gaucher disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND
Results of recent studies have demonstrated that genetic variants of the enzyme steroid 5α reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites ...such as conjugates of androstane-3α,17β-diol-glucuronide (3α-diol-G). However, this association was not consistently found among different ethnic groups. Thus, we aimed to determine whether the association with SRD5A2 genetic variations exists in a cohort of healthy Chinese elderly men, by examining 2 metabolite conjugates: androstane-3α,l7β-diol-3-glucuronide (3α-diol-3G) and androstane-3α,17β-diol-17-glucuronide (3α-diol-17G).
METHODS
We used GC-MS and LC-MS to measure serum sex steroid concentrations, including testosterone and dihydrotestosterone, and 3α-diol-3G and 3α-diol-17G in 1182 Chinese elderly men age 65 and older. Genotyping of the 3 SRD5A2 tagSNPs rs3731586, rs12470143, and rs523349 (V89L) was performed by using melting-temperature–shift allele-specific PCR.
RESULTS
The well-described SRD5A2 missense variant rs523349 (V89L) was modestly associated with the 3α-diol-17G concentration (P = 0.040). On the other hand, SNP rs12470143 was found to be significantly correlated with 3α-diol-3G concentration (P = 0.021). Results of haplotype analysis suggested that the presence of an A-C-G haplotype leads to an increased 3α-diol-3G concentration, a finding consistent with results of single SNP analysis.
CONCLUSIONS
The genetic variation of SRD5A2 is associated with circulating 3α-diol-3G and 3α-diol-17G concentrations in Chinese elderly men. In addition, we showed that SRD5A2 haplotypic association, rather than a single SNP alone, might be a better predictor of the 3α-diol-G concentration. Thus, the effect of either the haplotype itself or of other ungenotyped SNPs in linkage disequilibrium with the haplotype is responsible for the interindividual variation of 3α-diol-G.
Background: Alzheimer's disease (AD) is a neurodegenerative disease with a higher prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been identified throughout the brain. Owing to ...the putative neuroprotective effects of estrogen, estrogen receptor gene is a potential candidate modulating the development of AD. Preliminary associations between two polymorphisms of ESR1 (PvuII and XbaI) gene and AD have been reported. Methods: In this study, 16 single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database) were investigated to further evaluate the association between ESR1 polymorphisms and the risk of AD in the Chinese population. Results: A total of 233 Chinese AD patients and 245 age-matched elderly control subjects were recruited. Genetic associations were analyzed by chi-square test and interaction effect was analysed by logistic regression analysis. Five SNPs (clustered between intron 3 and intron 7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035); another two SNPs (located on exon 2 and intron 2) were shown to modulate the age-at-onset (AAO) in AD (p-value = 0.036 and 0.011). Conclusions: ESR1 gene polymorphisms may be associated with the AAO in AD. The present results provided information for possible associations between certain polymorphisms of ESR1 gene and the risk of AD.
Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C‐to‐T polymorphism at position −159 of CD14 was associated with serum total IgE level ...in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/−159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme‐linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty‐eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen‐specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/−159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/−159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C−159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.
Telomere shortening has been shown to contribute to the pathogenesis of atherosclerosis directly or through influencing cardiovascular risk factors. We examined telomere length (TL) and change in ...ankle-brachial index (ABI) over 5 years in a Chinese population aged 65 years and older living in the community. Telomere length was determined using the quantitative polymerase chain reaction (PCR) method in 976 men and 1030 women. Ankle-brachial index was measured using Doppler ultrasound. Analysis of covariance was used to examine the relationship between quartiles of TL and baseline ABI values as well as percentage change in ABI, adjusting for confounders. Women had longer TL and lower ABI values compared with men, and there was a significant trend for an inverse association between TL and percentage decline in ABI after adjustment for confounders. No significant association was observed in men. The findings support the association between TL and markers of atherosclerosis in older women but not men.
The diagnosis of glycogen storage disease (GSD) type IX is often complicated by the complexity of the phosphorylase kinase enzyme (PHK), and molecular analysis is the preferred way to provide ...definitive diagnosis. Here we reported two novel mutations found in two GSD type IX patients with different residual enzyme activities from Hong Kong, China using genetic analysis and, provided the molecular interpretation of the deficient PHK activity. These two newly described mutations would be useful for the study of future GSD patients.
The International Study of Asthma and Allergies in Childhood found that asthma affected 7% to 10% of Hong Kong schoolchildren.1 Overproduction of TH2-related cytokines is an important feature of ...asthmatic airway inflammation.2 Thymus and activation-regulated chemokine (TARC) is a key chemokine for attracting TH2 lymphocytes into sites of allergic inflammation.3,4 Our research group has recently found plasma TARC concentrations to be related to chronic and acute asthma in children.5,6 TARC was also released into the bronchoalveolar lavage fluid of asthmatic patients who underwent segmental allergen bronchoprovocation.3 The gene encoding TARC (TARC) is located on chromosomal region 16q13.7 Polymorphism screening of the coding and promoter regions of TARC revealed 3 single nucleotide polymorphisms (SNPs).8 Among these, the mutant -431T in the TARC promoter (accession no. Characteristicslow * Asthmatic patients Control subjects Age (y) 10.1±3.8 10.6±4.9 Male sex (n %) 182 (65) 64 (61) Serum log-transformed total IgE concentration (kIU/L) 2.59±0.62dagger 1.83±0.79 Atopy (>=1 specific IgE) (n %) 252 (89)dagger 48 (46) Sensitization (specific IgE) to aeroallergens   D pteronyssinus (n %) 247 (88)dagger 46 (44) Mixed cockroaches (n %) 79 (28)double dagger 16 (15) Cat (n %) 41 (15)§ 3 (3) PB eosinophils (% of total leukocytes)|| 7.5±4.7dagger 3.5±3.1 Spirometric variables   FEV1 (% predicted) 97±20 ND FEV1/FVC (%) 78±11 ND Table I Demographics and clinical characteristics in 282 asthmatic patients and 105 control subjects PB, Peripheral blood; ND, not done; FVC, forced vital capacity.
Telomeres and the ageing process Woo, Jean; Suen, Eddie; Tang, Nelson LS
Reviews in clinical gerontology,
02/2010, Letnik:
20, Številka:
1
Journal Article
Summary
Telomere length is a reflection of cumulative oxidative and inflammatory stress throughout the life course, as well as oestrogen exposure. There is evidence that telomere length is associated ...with lifespan; however, it does not appear to be a better indicator of biological age than chronological age, even though it can be considered a biomarker of ageing. There are studies showing association between leukocyte telomere length and many of the common diseases of ageing, lifestyle factors and socioeconomic status. However, the associations are less marked among older people. Research in the area of manipulation of genetic control of telomerase activity controlling telomere length may have clinical applications in future.
Mannose‐binding lectin (MBL), a member of the innate immune system, initiates complement deposition on microbial surfaces. MBL deficiency is associated with severe respiratory infections. ...Polymorphisms in the MBL gene (mbl2) were associated with the susceptibility and severity of autoimmune diseases. This study investigated whether mbl2 polymorphisms at positions ‐550 and ‐221 and at codon‐54 are associated with asthma phenotypes in Chinese children. Asthmatics aged 5–18 yr and non‐allergic controls were eligible, and their plasma total and allergen‐specific immunoglobulin E (IgE) concentrations were measured by micro‐particle immunoassay and fluorescent enzyme immunoassay. mbl2 polymorphisms were genotyped by restriction fragment length polymorphism. Three hundred and seventeen asthmatic children and 140 controls were recruited, with their mean (s.d.) log‐transformed plasma total IgE being 2.61 (0.61) and 1.77 (0.77), respectively (p < 0.0001). Polymorphisms at ‐550 and codon‐54 (p < 0.0001 for both) but not at ‐221 (p = 0.534) of mbl2 were significantly associated with plasma MBL concentrations. mbl2 genotypes were not associated with asthma, atopy, sensitization to individual aeroallergens or spirometric variable. Subjects with LYB haplotype had the lowest plasma MBL concentrations (p < 0.0001), but two‐ and three‐loci mbl2 haplotypes were also not associated with asthma diagnosis. However, patients with LY and LYB haplotypes were less likely to be atopic (p = 0.006 and 0.031). Subjects with LY and LYA were also less likely to be sensitized to cockroach (p = 0.035 and 0.047). The latter three associations became insignificant when adjusted for multiple comparisons. Despite the importance of MBL in innate immunity, our mbl2 polymorphisms only show weak association with asthma and atopy in children.
Early growth response‐1 (Egr‐1) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin‐13‐induced inflammation in ...mice. We investigated the effects of Chinese‐tagging single nucleotide polymorphisms (SNPs) of Egr‐1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (−4071 A→G) and three additional SNPs (−1427 C→T, −151 C→T and IVS1 −42 C→T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and −4071 A→G (p = 0.008) and IVS1 −42 C→T (p = 0.027) in asthmatic patients. After Bonferroni correction, only −4071 A→G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient β of 0.156 (95% CI: 0.046–0.317; p = 0.009) in asthmatics among the three SNPs with age and gender‐adjusted. In −4071 A→G, IgElog was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, −4071 A→G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5‐fold risk of having atopy and a 2.0‐fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr‐1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr‐1 inhibitors.
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