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1.
Tel'nov VI 《Genetika》2005,41(1):85-92
The role of genetic factors in the development of chronic radiation disease (CRD), mostly caused by occupational external gamma-exposure, was evaluated. The data of molecular genetic survey of a cohort of 985 workers at the nuclear power plant, the Mayak PA, were analyzed. Among the genetic markers tested, an association between the haptoglobin (Hp) genetic system and the development of CRD was established. It was demonstrated that the contribution of genetic factors to the CRD onset was realized not within the whole, but in a relatively narrow dose interval (70 to 400 cGy), i.e., was relative. Furthermore, at equal irradiation doses, relatively higher risk of CRD was observed among the Hp 2-2 phenotype carriers (1.96) compared to lower risk among the Hp 1-1 and Hp 2-1 phenotype carriers (0.64). It was shown that with the increase of the irradiation dose, genotypic differences in the CRD frequency decreased to the point of their complete disappearance. Comparison of the roles of the genetic factors in the onset of such deterministic irradiation effect as CRD, with their roles in the onset of lung cancer in tobacco smokers revealed similar patterns. A scheme of the relationships between the effector intensity and the differences in the genetically determined radioresistance is presented. The data obtained do not support the idea that the survivals of the atomic bombing of Hiroshima and Nagasaki were the most radioresistant individuals, who are not representative for evaluating the radiation risk. 相似文献
2.
AIMS:
The aim of this study was to investigate the association between haptoglobin (Hp) phenotypes and risk of the development of diabetic retinopathy (DR) in patients of type 2 diabetes mellitus.MATERIALS AND METHODS:
This cross-sectional study included 45 normotensive type 2 diabetic patients (duration more than 5 years) admitted in the hospital divided into two groups (with and without DR) on the basis of fundus examination by direct ophthalmoscopy. Serum samples of all patients were subjected for Hp phenotyping by polyacrylamide gel electrophoresis.RESULTS:
DR was associated significantly in diabetic patients with Hp2-2 phenotype (79.31%) than diabetic patients with Hp2-1 phenotype (43.75%) and Hp2-2 had higher odds ratio (OR) for DR in univariate analysis (OR 4.929, [95% confidence interval [CI] (1.297-18.733)], P = 0.016) and multivariate analysis (OR 7.704 [95% CI (0.887-66.945)], P = 0.064). Furthermore, Hp2-2 was associated significantly with severe forms of DR.CONCLUSION:
Hp2-2 phenotype is associated with susceptibility to DR showing a graded risk relationship to the number of Hp2 alleles. Determination of Hp phenotype may be useful in the risk assessment and management of DR. 相似文献3.
Shevchenko VA 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2000,40(5):630-639
The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions. 相似文献
4.
Mathilde Savy Branwen J. Hennig Conor P. Doherty Anthony J. Fulford Robin Bailey Martin J. Holland Giorgio Sirugo Kirk A. Rockett Dominic P. Kwiatkowski Andrew M. Prentice Sharon E. Cox 《PloS one》2010,5(6)
Background
Susceptibility and resistance to trachoma, the leading infectious cause of blindness, have been associated with a range of host genetic factors. In vitro studies of the causative organism, Chlamydia trachomatis, demonstrate that iron availability regulates its growth, suggesting that host genes involved in regulating iron status and/or availability may modulate the risk of trachoma. The objective was to investigate whether haptoglobin (Hp) haplotypes constructed from the functional polymorphism (Hp1/Hp2) plus the functional promoter SNPs -61A-C (rs5471) and -101C-G (rs5470), or sickle cell trait (HbAS, rs334) were associated with risk of active trachoma when stratified by age and sex, in rural Gambian children.Methodology and Principal Findings
In two cross sectional surveys of children aged 6–78 months (n = 836), the prevalence of the clinical signs of active trachoma was 21.4%. Within boys, haplotype E (-101G, -61A, Hp1), containing the variant allele of the -101C-G promoter SNP, was associated with a two-fold increased risk of active trachoma (OR = 2.0 [1.17–3.44]). Within girls, an opposite association was non-significant (OR = 0.58 [0.32–1.04]; P = 0.07) and the interaction by sex was statistically significant (P = 0.001). There was no association between trachoma and HbAS.Conclusions
These data indicate that genetic variation in Hp may affect susceptibility to active trachoma differentially by sex in The Gambia. 相似文献5.
6.
Background
Cerebral cavernous malformations (CCM) present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members.Methods
We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old) sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives.Results
The phenotypes of cerebral cavernous malformations (CCMs) in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA.Conclusions
Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.7.
Tracey L. Weissgerber Robin E. Gandley Paula L. McGee Catherine Y. Spong Leslie Myatt Kenneth J. Leveno John M. Thorp Jr Brian M. Mercer Alan M. Peaceman Susan M. Ramin Marshall W. Carpenter Philip Samuels Anthony Sciscione Margaret Harper Jorge E. Tolosa George Saade Yoram Sorokin for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network 《PloS one》2013,8(4)
Haptoglobin’s (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61–6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia. 相似文献
8.
DNA polymorphisms in the controlling region of the human haptoglobin genes: a molecular explanation for the haptoglobin 2-1 modified phenotype. 总被引:1,自引:0,他引:1
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N Maeda 《American journal of human genetics》1991,49(1):158-166
A haptoglobin 2-1 modified (Hp2-1mod) phenotype results when the amount of Hp2 polypeptide synthesized in Hp2/Hp1 heterozygotes is less than that of Hp1 polypeptide. Cloned Hp2 DNA from an individual with the Hp2-1mod phenotype is here shown to have a C in place of the normal A at nucleotide position -61 in one of the interleukin-6 (IL-6) responsive elements of the haptoglobin promoter region. Direct sequencing of the haptoglobin promoter region, amplified by PCR, from DNA from unrelated American blacks showed a C at -61 in all of 10 individuals with the Hp2-1mod phenotype, in two of four with a "possible Hp2-1mod" phenotype, but in none of 15 with the Hp2-1 phenotype. Thus the -61C mutation in the Hp2-61C allele is strongly associated with the Hp2-1mod phenotype. Sequencing results also show that there are three other promoter sequences in the population studied; each can be associated with either Hp2 or Hp1. The variability seen in the Hp2-1mod phenotype, a variability which ranges from close to Hp2-1 to close to Hp1-1, can be explained, in part, by the existence of several Hp2 alleles differing in their promoters--and possibly, in part, by differences in the promoters of the accompanying Hp1 allele. A further part of the variability may be the consequence of differences in the way that the Hp2-61C and the Hp2 alleles respond to the IL-6-dependent factor during an acute-phase response. 相似文献
9.
Bernard D Christophe A Delanghe J Langlois M De Buyzere M Comhaire F 《Redox report : communications in free radical research》2003,8(1):41-46
The genetic polymorphism of haptoglobin (Hp) is an independent risk factor in the pathogenesis of atherosclerosis, a condition in which decreased resistance to in vitro oxidation of LDL-cholesterol is observed. We hypothesised that the Hp polymorphism is one of the factors modulating the resistance to Cu(2+)-induced oxidation of LDL during antioxidant supplementation. In this study, 74 middle-aged subjects with increased oxidative stress were allocated to either matched placebo or oral antioxidative treatment (Quatral) once daily for 16 weeks. Study parameters were increase of lag phase (DeltaLAG) and the ratio of lag phase during treatment period versus baseline (relative oxidation resistance, ROR), measured by Cu(2+)-induced oxidation of isolated LDL. Hp phenotypes were determined by starch gel electrophoresis. A significant and persistent increase of DeltaLAG (P < 0.05) and ROR (P < 0.01) were observed after 16 weeks of active treatment versus placebo. Interindividual differences in both parameters were significantly associated with the Hp polymorphism: in the active treatment group, DeltaLAG and ROR were significantly higher in Hp 1-1 subjects (P < 0.01) compared to Hp 2-1 and 2-2. Our data demonstrate that Hp phenotype is one of the modulating factors determining the increased resistance to Cu(2+)-induced oxidation of LDL during antioxidative treatment. 相似文献
10.
Sigrid B Sando Stacey Melquist Ashley Cannon Michael L Hutton Olav Sletvold Ingvild Saltvedt Linda R White Stian Lydersen Jan O Aasly 《BMC neurology》2008,8(1):9
Background
The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD) in central Norway. The APOE ε4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on the risk and the age at onset of AD in this population.Methods
376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated.Results
Odds Ratio (OR) for developing AD was significantly increased in carriers of the APOE ε4 allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9 in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by APOE ε4 alleles.Conclusion
APOE ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.11.
Sukaina Al-balaghee Zeinab Al-balaghee Ashraf Shabani Parinaz Ghadam Mojgan Bandehpour Ali Askari Mehr Bahram Kazemi 《Reports of Biochemistry & Molecular Biology》2015,3(2):51-55
Background:
Haptoglobin (Hp) is a plasma α2-sialoglycoprotein that contains alpha and beta chains. It displays in three common phenotypes, Hp1-1, Hp2-1, and Hp2-2. Proteins expressed by polymorphic genes have grossly different molecular sizes resulting in different diffusion rates in the brain. Haptoglobin expressed by the Hp2-2 genotype has lower hemoglobin-binding capacity than Hp1-1 or Hp2-1 and is associated with idiopathic generalized epilepsy.Methods:
To determine polymorphism in haptoglobin genes in patients with idiopathic generalized tonic-clonic seizures, 42 men, 42 women, and 50 controls were selected for this study. Genomic DNA was extracted from blood and studied by polymerase chain reactions (PCR).Results:
The amplified fragments for the Hp1-1 and Hp2-2 genotypes were 1757 and 3481 base pairs (bp) respectively, and the Hp2-1 genotype had both fragments, in addition to a 349-bp fragment. The distribution of the three major Hp phenotypes in epilepsy patients was 28.6 (1-1), 38.1 (2-1), and 33.3% (2-2) in the men, and 31 (1-1), 40.5 (2-1), and 28.6% (2-2) in the women. The distribution of Hp genotypes in controls was 22 (1-1), 40 (2-1), and 38% (2-2).Conclusion:
We show that all Hp genotypes participate in idiopathic generalized epilepsy.Key Words: Epilepsy, Haptoglobin, Iran 相似文献12.
BACKGROUND:
Gujarat is located at the western most point of the Indian subcontinent. Valsad and Surat districts are part of the ‘tribal belt’of Gujarat and constitute 29.1% of total tribal population of Gujarat. These tribal populations are a rich source of gaining insights in the patterns of genetic diversity and genetico-environmental disorders against the back drop of their ecological, historical and ethnographic aspects.AIM:
The objectives were to find out a) the genetic diversity among the tribes of Gujarat with reference to haptoglobin (Hp) locus b) the relationship between Hp polymorphism and sickle cell anemia/trait.MATERIALS AND METHODS:
431 individuals belonging to eight tribal groups were studied for Hp polymorphism using polyacrylamide disc gel electrophoresis (PAGE). Hb*S was screened by dithionate tube turbididy (DTT) test and confirmed using cellulose acetate membrane electrophoresis (CAME).STATISTICAL ANALYSIS:
Allele frequency was calculated by direct gene counting method. Average heterozygosity and gene diversity were computed using software DISPAN. Analysis of molecular variance (AMOVA) was estimated using software ARLEQUIN version 3.1.RESULTS AND CONCLUSIONS:
Pattern of allele frequency distribution showed preponderance of Hp2 allele in all the eight tribal groups, which is in accordance with its frequency in different populations of Indian subcontinent. Total average heterozygosity (HT) was found to be low (0.160) but the level of genetic differentiation (GST) was found to be moderately high (5.6%). AMOVA analysis indicated least among group variance between west and south Indian populations (-0.04%) indicating the affinities of the tribes of Gujarat with that of Dravidian speaking groups. Analysis of Hp phenotypes among sickle cell anemia/ trait individuals revealed a high frequency of Hp 0-0 phenotype (92.7%) among SS individuals as opposed to only 9.7% among AS individuals, reaffirming the selective advantage of HbAS state in relation to hemolytic disorders. 相似文献13.
Beata Jurecka-Lubieniecka Rafal Ploski Dorota Kula Konrad Szymanski Tomasz Bednarczuk Urszula Ambroziak Kornelia Hasse-Lazar Lidia Hyla-Klekot Andrzej Tukiendorf Zofia Kolosza Barbara Jarzab 《PloS one》2014,9(7)
Background
Graves'' orbitopathy (GO) as well as Graves'' disease (GD) hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR). GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age), for whom environmental effects had less time to influence outcomes than in adults.Methods
768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2). Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4) and lymphoid protein tyrosine phosphatase (PTPN22).Results
The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole.Conclusions
Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients. 相似文献14.
Ferens-Sieczkowska M Midro A Mierzejewska-Iwanowska B Zwierz K Katnik-Prastowska I 《Glycoconjugate journal》1999,16(10):573-577
Alterations in haptoglobin (Hp) glycosylation were examined in the plasma of the first patient with carbohydrate-deficient glycoprotein syndrome (CDGS) who was described in Poland. Hp concentration in the CDGS patient plasma was low (240mg/l) and the Hp phenotype was shown to be 2-2. Three glycoforms of the Hp subunit were observed in SDS-PAGE in CDGS. The densitometric analysis and molecular weight determinations suggested that 50% of glycoforms were fully glycosylated; 30% contained three out of four and 20% only two out of four glycan units compared to those that are present in Hp derived from healthy people. Results with lectins (concanavalin A and Sambucus nigra, Maackia amurensis and Alleuria aurantia agglutinins) indicate that all three glycoforms of subunit of CDGS-Hp contained biantennary complex glycans terminated with 2,6 bound sialic acid, but without fucose or 2,3 linked sialic acid. Hp glycosylation abnormalities described in this work suggest that this case was a type I carbohydrate-deficient glycoprotein syndrome. 相似文献
15.
The efficacy of Sizofiran(SPG), a highly purified -1,3-D-glucan from the culture broth of a basidiomycetesSchizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of OH/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected im at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C-treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy. 相似文献
16.
Purpose
Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL) has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure.Materials/Methods
C57BL6 mice received a single whole body or partial body irradiation dose of 1–8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1–3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose.Results
At all doses between 1–8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation.Conclusion
Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice. 相似文献17.
Kobashigawa S Suzuki K Yamashita S 《Biochemical and biophysical research communications》2011,414(4):795-800
Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial . Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation. 相似文献
18.
Su YN Hung CC Lin SY Chen FY Chern JP Tsai C Chang TS Yang CC Li H Ho HN Lee CN 《PloS one》2011,6(2):e17067
Background
Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25–50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program.Methods and Findings
This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968.Conclusion
The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling. 相似文献19.
Olena Pavlyushchik Viktor Afonin Svetlana Fatykhava Polina Shabunya Viktoryia Sarokina Aliaksandr Khapaliuk 《Biological trace element research》2017,179(1):110-116
Growth hormone (GH) and zinc (Zn) were evaluated for their potential to prevent radiation injury using a rat model of radiation-induced skin injury. Sprague–Dawley rats were divided into five groups: a control group not receiving Zn, GH, or irradiation: a radiation (RT) group receiving a single 30 Gy dose of gamma irradiation to the right hind legs; a radiation + GH group (RT + GH) receiving a single 30 Gy dose of gamma irradiation plus the subcutaneous administration of 0.01 IU kg d?1 GH; a radiation + Zn group (RT + Zn) receiving a single 30 Gy dose plus 5 mg kg d?1 Zn po; and a radiation + GH + Zn group (RT + GH + Zn) group receiving a single 30 Gy dose plus subcutaneous 0.01 IU kg d?1 GH and 5 mg kg d?1 Zn po. Acute skin reactions were assessed every 3 days by two radiation oncologists grouping. Light microscopic findings were assessed blindly by two pathologists. Groups receiving irradiation were associated with dermatitis as compared to the control group (P < 0.05). The severity of radiodermatitis in the RT + GH, RT + Zn, and RT + GH + Zn groups was significantly lower than that in the RT group (P < 0.05). Furthermore, radiodermatitis was observed earlier in the RT group than in the other treatment groups (P < 0.05). GH and Zn effectively prevented epidermal atrophy, dermal degeneration, and hair follicle atrophy. The highest level of protection against radiation dermatitis was observed in the combination group. 相似文献
20.
This paper recapitulates the advances in the field of genetic risk estimation that have occurred during the past decade and using them as a basis, presents revised estimates of genetic risks of exposure to radiation. The advances include: (i) an upward revision of the estimates of incidence for Mendelian diseases (2.4% now versus 1.25% in 1993); (ii) the introduction of a conceptual change for calculating doubling doses; (iii) the elaboration of methods to estimate the mutation component (i.e. the relative increase in disease frequency per unit relative increase in mutation rate) and the use of the estimates obtained through these methods for assessing the impact of induced mutations on the incidence of Mendelian and chronic multifactorial diseases; (iv) the introduction of an additional factor called the "potential recoverability correction factor" in the risk equation to bridge the gap between radiation-induced mutations that have been recovered in mice and the risk of radiation-inducible genetic disease in human live births and (v) the introduction of the concept that the adverse effects of radiation-induced genetic damage are likely to be manifest predominantly as multi-system developmental abnormalities in the progeny.For all classes of genetic disease (except congenital abnormalities), the estimates of risk have been obtained using a doubling dose of 1 Gy. For a population exposed to low LET, chronic/ low dose irradiation, the current estimates for the first generation progeny are the following (all estimates per million live born progeny per Gy of parental irradiation): autosomal dominant and X-linked diseases, approximately 750-1500 cases; autosomal recessive, nearly zero and chronic multifactorial diseases, approximately 250-1200 cases. For congenital abnormalities, the estimate is approximately 2000 cases and is based on mouse data on developmental abnormalities. The total risk per Gy is of the order of approximately 3000-4700 cases which represent approximately 0.4-0.6% of the baseline frequency of these diseases (738,000 per million) in the population. 相似文献