共查询到20条相似文献,搜索用时 15 毫秒
1.
Lisong Shi Cong Li Chuchu Wang Yunlong Xia Gang Wu Fan Wang Chengqi Xu Pengyun Wang Xiuchun Li Dan Wang Xin Xiong Ying Bai Mugen Liu Jingyu Liu Xiang Ren Lianjun Gao Binbin Wang Qiutang Zeng Bo Yang Xu Ma Yanzong Yang Xin Tu Qing Kenneth Wang 《Human genetics》2009,126(6):843-849
Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting and an independent risk factor for stroke. Approximately 10 million Chinese people are affected by AF, but the genetic basis is largely unknown. A recent genome-wide association study in Iceland identified association between SNP rs2200733 on 4q25 and AF; however, many independent replication studies are essential to unequivocally validate this association. To assess the association between rs2200733 and AF as well as that between rs2200733 and ischemic stroke in a mainland Chinese Han population, we carried out case–control association studies with 383 AF patients versus 851 non-AF controls and 811 ischemic stroke patients versus 688 non-stroke controls. Highly significant association was detected between rs2200733 and AF in a Chinese Han population (allelic P = 3.7 × 10?11 with OR = 1.81; genotypic P = 4.1 × 10?12 with a dominant model). When the AF cases were divided into lone AF (32.6%) and other types of AF (67.4%), significantly stronger association was found with lone AF (OR = 2.40, P = 1.3 × 10?9 compared to OR = 1.59, P = 6.2 × 10?7 for other types of AF; P = 0.02 for two ORs). No significant association was found between rs2200733 and ischemic stroke. Our results suggest that SNP rs2200733 confers a highly significant risk of AF, but not ischemic stroke, in a more representative Chinese Han population in the mainland China. 相似文献
2.
Shamone R. Gore-Panter Jeffery Hsu Peter Hanna A. Marc Gillinov Gosta Pettersson David W. Newton Christine S. Moravec David R. Van Wagoner Mina K. Chung John Barnard Jonathan D. Smith 《PloS one》2014,9(1)
Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic. 相似文献
3.
Weixing Zheng Chenghui Yan Xiaohu Wang Zhurong Luo Fengping Chen Yuhui Yang Donglin Liu Xiaobo Gai Jianping Hou Mingfang Huang 《PloS one》2013,8(12)
Transforming growth factor-β1 (TGF-β1) is related to the degree of atrial fibrosis and plays critical roles in the induction and perpetuation of atrial fibrillation (AF). To investigate the association of the common promoter polymorphism rs1800469 in the TGF-β1 gene (TGFB1) with the risk of AF in Chinese Han population, we carried out a case-control study of two hospital-based independent populations: Southeast Chinese population (581 patients with AF and 723 controls), and Northeast Chinese population (308 AF patients and 292 controls). Two hundred and seventy-eight cases of AF were lone AF and 334 cases of AF were diagnosed as paroxysmal AF. In both populations, AF patients had larger left atrial diameters than the controls did. The rs1800469 genotypes in the TGFB1 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies of rs1800469 were not different between AF patients and controls of the Southeast Chinese population, Northeast Chinese population, and total Study Population. After adjustment for age, sex, hypertension and LAD, there was no association between the rs1800469 polymorphism and the risk of AF under the dominant, recessive and additive genetic models. Similar results were obtained from subanalysis of the lone and paroxymal AF subgroups. Our results do not support the role of the TGFB1 rs1800469 functional gene variant in the development of AF in the Chinese Han population. 相似文献
4.
Hailong Cao Qing Zhou Rongfang Lan Oluf Dimitri R?e Xin Chen Yijiang Chen Dongjin Wang 《PloS one》2014,9(11)
Transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509T polymorphism (rs1800469) was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR) = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509T allele than that of the -509C allele. In conclusion, the TGF-β1 C-509T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF. 相似文献
5.
Higgins CD Swerdlow AJ Schoemaker MJ Wright AF Jacobs PA;UK Clinical Cytogenetics Group 《Human genetics》2007,121(6):691-696
The mortality and cancer incidence risks among males with Y polysomy are unknown because there have been no large long-term
cohort studies carried out of such men. We conducted a cohort study of 667 men diagnosed with the abnormality in Britain since
1959 to compare their mortality and cancer incidence rates with those of the general population. Sixty deaths occurred during
follow-up to December 2005, twice the number expected from general population rates (standardised mortality ratio (SMR) = 2.0
(95% confidence interval (CI) 1.5–2.6)). Significantly raised mortality was observed for diseases of the nervous system (SMR = 7.0,
95% CI: 2.3–16.4), circulatory system (SMR = 2.1, 95% CI: 1.3–3.2), respiratory system (SMR = 4.0, 95% CI: 1.8–7.5), genitourinary
system (SMR = 10.2, 95% CI: 1.2–36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2–30.5). Four of the five nervous system
deaths were from epilepsy, the risk of death from this condition being more than 20-fold raised. The rates of cancer incidence
and mortality among these men was not significantly different from those in the general population. This study provides evidence
that mortality rates from several specific causes are raised among men with Y polysomy. The use of these data in genetic counselling
should be cautious particularly for cases of Y polysomy that are detected prenatally. Further investigations are required
to confirm these findings and to elucidate the possible role of genes on the Y chromosome in the aetiology of these causes
of death. 相似文献
6.
Xeroderma pigmentosum group A (XPA) participates in modulating recognition of DNA damage during the DNA nucleotide excision
repair process. The XPA A23G polymorphism has been investigated in case–control studies to evaluate the cancer risk attributed to the variant, but
the results were conflicting. To clarify the effect of XPA A23G polymorphism in cancer risk, we conducted a meta-analysis that included 30 published case–control studies. Overall,
no significant association of XPA A23G variant with cancer susceptibility was observed for any genetic model. However, significant
association was observed for colorectal cancer (GG vs. AA: OR = 1.68, 95% CI = 1.15–2.44; dominant genetic model GG + AG vs.
AA: OR = 1.54, 95% CI = 1.08–1.17), for breast cancer an increased but non-significant risk was found (GG vs. AA: OR = 1.27,
95% CI = 0.98–1.66; dominant genetic model GG + AG vs. AA: OR = 1.27, 95% CI = 0.99–1.63), and for head and neck cancer an
increased risk was observed in recessive model (OR = 1.19, 95% CI = 1.02–1.38), whereas for lung cancer a significant reduced
risk was observed (GG vs. AA: OR = 0.77, 95% CI = 0.66–0.90; dominant genetic model GG + AG vs. AA: OR = 0.76, 95% CI = 0.66–0.87),
it’s noting that in Asian population the inverse association was more apparent. In addition, in Asian population for esophageal
cancer a significant decreased risk was also found in dominant genetic model (OR = 0.55; 95% CI = 0.43–0.70) and for head
and neck cancer an increased risk was observed in dominant genetic model (OR = 1.51, 95% CI = 1.03–2.23). The meta-analysis
suggested that the XPA A23G G allele is a low-penetrant risk factor for cancer development. 相似文献
7.
Analysis of population changes by measurement of body weight in the Koshima troop of Japanese monkeys 总被引:5,自引:0,他引:5
Akio Mori 《Primates; journal of primatology》1979,20(3):371-397
Measurements of the body weight of monkeys in the Japanese monkey troop on Koshima islet in southern Japan have been made
since 1970. Population changes in the troop have been recorded since 1952. The population changes were further analyzed on
the basis of the body weight changes of the troop members. The recent history of the Koshima troop can be divided into three
periods differing according to conditions of artificial feeding: (1) a semi-wild period (SW Period, 1952–63); (2) an artificial
feeding period (AF Period, 1964–71); (3) and a restricted artificial feeding period (Non-AF Period, 1972–77). The AF Period
represented a period of population growth, whereas the Non-AF Period was a declining one when the population density of the
troop was roughly ten times that of most wild troops. These population changes, i.e., changes in population parameters especially
in the population declining phase, could be fairly well understood from the general features of the body weight changes of
the troop members, the slow body weight growth, elevation of age at first birth, and small size of adult females. Reproduction
and survival were affected by seasonal and yearly changes in body weight. The pattern of changes in body weight displayed
seasonal peaks in the autumn and spring. Of these, the former suggests that fruit eating in the autumn is an important factor
in the reproduction and growth of the monkeys. 相似文献
8.
Background
Atrial fibrillation (AF) is the most common sustained atrial arrhythmia and it is independently associated with an increased morbidity and mortality. As a result of the high prevalence of AF, the economic and clinical impact of the disease is substantial. This study describes the economic and clinical impact of AF in the Netherlands.Methods
Epidemiological data on AF in the Netherlands were projected on population estimates of the Netherlands in 2009 and combined with data on the cost of AF and its interventions.Results
Overall prevalence of AF in the Netherlands is 5.5% in the population over 55 years, corresponding to about 250,000 AF patients. The prevalence increases with age, and the mean age of AF patients is 69.3 years. Incidence of AF in the Netherlands varies with age, from 1188 new cases in the age group of 55 to 59 up to 7074 new cases in the age group 75 to 79. Total new cases amounts to 45,085 patients per year in the Netherlands. Total costs of AF in the Netherlands are € 583 million, of which the majority (70%) were accounted for by hospitalisations and in-hospital procedures. Pharmacotherapeutic management of AF totalled € 17 million in the Netherlands in 2009.Discussion
AF is a serious disease with a high clinical and economic burden, especially due to hospitalisations as a result of cardiovascular events. The number of patients with AF in the Netherlands is considerable and will increase with the ageing population in the future. 相似文献9.
Guazzi M Berti M Belletti S Reina G Guazzi MD 《American journal of physiology. Heart and circulatory physiology》2006,291(5):H2396-H2402
Exercising muscle hypoperfusion stimulates afferents (metaboreceptors) involved in the regulation of ventilation. Atrial fibrillation (AF), particularly when combined with diseases causing endothelial (ED) impairment, such as hypertension (HP) and diabetes mellitus (DM), depresses the ED activity and enhances exercise hyperventilation. The relationship between these two functions and the underlying mechanisms have not been explored previously. In lone AF or AF associated with HP or DM (12 subjects in each cohort), we investigated the brachial artery flow-mediated dilatation (ED function) and ventilation during the recovery phase of handgrip (metaboreflex) exercise for subjects receiving placebo or oral vitamin C (double-blind crossover), both before and after cardioversion (CV) to sinus rhythm. Baseline ED impairment was increasingly more severe and the ergoreflex activity more pronounced in AF + HP and AF + DM compared with lone AF. Vitamin C and CV significantly improved both flow-mediated dilatation and metaboreflex activity in lone AF and AF + HP, and vitamin C did not produce any additive effect when administered after CV. In AF + DM, neither vitamin C nor CV was effective. This study provides the following information: AF generates oxidative injury, which is less when the arrhythmia is lone AF and greater when the arrhythmia is associated with HP. In DM, the oxidative injury generated by AF is refractory to a rather weak antioxidant, like vitamin C, or the baseline damage is such as to prevent any additive influence of AF. In AF, a cause-effect link exists between ED dysfunction and metaboreflex activity. Ventilatory advantages of CV seem to be inversely related with the extension of the underlying ED oxidative impairment. 相似文献
10.
Li-qun Zhao Zu-jia Wen Yong Wei Juan Xu Zheng Chen Bao-zhen Qi Zhi-ming Wang Yong-yong Shi Shao-wen Liu 《PloS one》2015,10(2)
BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor. 相似文献
11.
Göran K Olivecrona Bjarne Madsen Härdig Anders Roijer Mattias Block Edgars Grins Hans W Persson Leif Johansson Bertil Olsson 《BMC cardiovascular disorders》2005,5(1):1-10
Background
Natural history of paroxysmal atrial fibrillation (AF) is not very well documented. Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30% over a period of 1–3 years. We performed an epidemiologic study to elucidate the natural history of paroxysmal AF, this study estimated its incidence in a general practice setting, identified associated factors and analyzed the progression into chronic AF as well as the mortality rate.Methods
Using the UK General Practice Research Database (GPRD), we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996. Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner (GP) and a random sample of controls. We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF.Results
The incidence of paroxysmal AF was 1.0 per 1,000 person-years. Major risk factors for paroxysmal AF were age and prior valvular heart disease, ischaemic heart disease, heart failure and hyperthyroidism. During a mean follow-up of 2.7 years, 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF. Risk factors associated with progression were valvular heart disease (OR 2.7, 95% CI 1.2–6.0) and moderate to high alcohol consumption (OR 3.0, 95% CI 1.1–8.0). Paroxysmal AF patients did not carry an increased risk of mortality, compared to an age and sex matched sample of the general population. There was a suggestion of a small increased risk among patients progressing to chronic AF (RR 1.5, 96% CI 0.8–2.9).Conclusion
Paroxysmal AF is a common arrhythmia in the general practice setting, increasing with age and commonly associated with other heart diseases. It sometimes is the initial presentation and then progress to chronic AF. A history of valvular heart disease and alcohol consumption are associated with this progression. 相似文献12.
Andreas Fiebig Petra Krusche Andreas Wolf Michael Krawczak Birgitt Timm Susanna Nikolaus Norbert Frings Stefan Schreiber 《Human genetics》2010,127(6):669-674
Varicose veins without skin changes have a prevalence of approximately 20% in Northern and Western Europe whereas advanced
chronic venous insufficiency affects about 3% of the population. Genetic risk factors are thought to play an important role
in the aetiology of both these chronic venous diseases (CVD). We evaluated the relative genetic and environmental impact upon
CVD risk by estimating the heritability of the disease in 4,033 nuclear families, comprising 16,434 individuals from all over
Germany. Upon clinical examination, patients were classified according to the CEAP guidelines as either C2 (simple varicose
veins), C3 (oedema), C4 (skin changes without ulceration), C5 (healed ulceration), or C6 (active ulcers). The narrow-sense
heritability (h
2) of CVD equals 17.3% (standard error 2.5%, likelihood ratio test P = 1.4 × 10−13). The proportion of disease risk attributable to age (at ascertainment) and sex, the two main risk factors for CVD, was estimated
as 10.7% (Kullback–Leibler deviance R
2). The heritability of CVD is high, thereby suggesting a notable genetic component in the aetiology of the disease. Systematic
population-based searches for CVD susceptibility genes are therefore warranted. 相似文献
13.
Motoyuki Nakamura Yorihiko Koeda Fumitaka Tanaka Toshiyuki Onoda Kazuyoshi Itai Masaki Ohsawa Kozo Tanno Kiyomi Sakata Shinich Omama Yasuhiro Ishibashi Shinji Makita Mutsuko Ohta Kuniaki Ogasawara Takashi Komatsu Akira Okayama 《PloS one》2013,8(12)
Objectives
Atrial fibrillation (AF) is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV) events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP) and CV risk in real world AF subjects remains unknown.Methods
The subject of the study (n = 228; mean age = 69 years) was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%). The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score). In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) indices.Results
During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years). The event-free ratio was significantly lower in the highest tertile (p < 0.02). After adjustment for established CV risk factors, the hazard ratio (HR) of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p < 0.05).Conclusion
Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects. 相似文献14.
Knottnerus IL Gielen M Lodder J Rouhl RP Staals J Vlietinck R van Oostenbrugge RJ 《PloS one》2011,6(6):e21439
Background
Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke.Methods
By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated.Principal Findings
We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45–3.53) for overall first-degree relatives, 4.52 (95%CI 3.61–5.65) for patients'' parents and 2.10 (95%CI 1.63–2.69) for patients'' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size.Conclusions
We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke. 相似文献15.
Christian Selmer Morten Lock Hansen Jonas Bjerring Olesen Charlotte Mérie Jesper Lindhardsen Anne-Marie Schjerning Olsen Jesper Clausager Madsen Ulla Schmidt Jens Faber Peter Riis Hansen Ole Dyg Pedersen Christian Torp-Pedersen Gunnar Hilmar Gislason 《PloS one》2013,8(2)
Aims
To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism.Methods and Results
All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done.Conclusion
New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted. 相似文献16.
Vasileios Papadopoulos Ioannis Mitroulis Stavros Giaglis 《Molecular biology reports》2010,37(1):355-358
Turkey is one of the few countries in the world where Familial Mediterranean Fever (FMF), an autoinflammatory disease caused
by mutations in MEFV, the gene encoding pyrin, is not rare. Many interesting studies regarding the genetics of Familial Mediterranean Fever in
Turkey have been already published. Despite that different MEFV genetic profiles have been revealed for Turkish FMF patients, deriving from different regions of Turkey, a systematic population
genetics analysis has not been carried out yet. The present study aims to investigate the population genetics of MEFV in Turkish FMF patients so as to additionally facilitate the clinical interpretation of individualized genetic data. All
relevant studies have been recruited by searching PubMed with the terms “MEFV”, “FMF”, and “Turkey”. Seven of them, including
3,061 FMF patients, contained all necessary data concerning allelic and genotypic frequencies of the 4 commonest MEFV mutations in Turkey (M694V, V726A, M680I, E148Q). From all 6,122 MEFV alleles analyzed, the M694V mutation was recognized in 15.6–52.2% (mean 29.3%), the V726A in 1.5–9.7% (mean 4.8%), the M680I
in 1.5–15.5% (mean 7.6%), and the E148Q in 3.2–13.9% (mean 5.5%). Unidentified mutations ranged from 0–42.9% (mean 16.8%).
No mutations were found in 0–54.5% (mean 36.0%) of the patients. The allelic and genotypic frequencies of the most frequent
mutation (M694V) showed aberration of the Hardy–Weinberg law for all 7 populations studied. By application of the Arlequin
2.0 population genetics software, the Fixation index (F
ST) was found to be 0.09994, thus demonstrating that the observed variability is mainly within (90.006%) and not among (9.994%)
populations (P < 0.00001). Moreover, the global test of differentiation demonstrated that every population differs from each other (P < 0.00325). Finally, the Ewens–Watterson test of selective neutrality yielded to statistical significance in only 3 populations.
In conclusion, Turkish FMF patients are characterized by an increased genetic heterogeneity, explained by the intrapopulation
differentiation. Thus, the regional origin should be regarded as a determining factor in the diagnosis of FMF in Turkish patients. 相似文献
17.
The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of
acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed
the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies
containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID
users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis.
Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI]
1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative
AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11).
In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective
NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen,
supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so
further investigation into the risk of AMI is warranted because the potential for harm can be substantial. 相似文献
18.
van der Walt JM Scott WK Slifer S Gaskell PC Martin ER Welsh-Bohmer K Creason M Crunk A Fuzzell D McFarland L Kroner CC Jackson CE Haines JL Pericak-Vance MA 《Human genetics》2005,118(1):115-122
Old Order Amish, founded by a small number of Swiss immigrants, exist in culturally isolated communities across rural North America. The consequences of genetic isolation and inbreeding within this group are evident by increased frequencies of many monogenic diseases and several complex disorders. Conversely, the prevalence of Alzheimer disease (AD), the most common form of dementia, is lower in the Amish than in the general American population. Since mitochondrial dysfunction has been proposed as an underlying cause of AD and a specific haplogroup was found to affect AD susceptibility in Caucasians, we investigated whether inherited mitochondrial haplogroups affect risk of developing AD dementia in Ohio and Indiana Amish communities. Ninety-five independent matrilines were observed across six large pedigrees and three small pedigrees then classified into seven major European haplogroups. Haplogroup T is the most frequent haplogroup represented overall in these maternal lines (35.4%) while observed in only 10.6% in outbred American and European populations. Furthermore, haplogroups J and K are less frequent (1.0%) than in the outbred data set (9.4–11.2%). Affected case matrilines and unaffected control lines were chosen from pedigrees to test whether specific haplogroups and their defining SNPs confer risk of AD. We did not observe frequency differences between AD cases compared to controls overall or when stratified by sex. Therefore, we suggest that the genetic effect responsible for AD dementia in the affected Amish pedigrees is unlikely to be of mitochondrial origin and may be caused by nuclear genetic factors. 相似文献
19.
Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating
a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer
mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates.
The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population
cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated
to be 1.93×10–2 Sv–1 (95% CI 1.14, 3.38), or 0.44 years of life lost Sv–1 (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36×10–2 Sv–1 (95% CI 8.41, 12.42), or 1.38 years of life lost Sv–1 (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods;
however, leukaemia risks were somewhat higher, by 10–35%, than those predicted by classical likelihood-based methods. This
is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of
measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted
by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which
form the basis of established estimates of radiation-induced cancer risk.
Received: 28 September 1999 / Accepted: 21 August 2000 相似文献
20.
Genetic prion disease: the EUROCJD experience 总被引:10,自引:0,他引:10
Kovács GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C Collins SJ Boyd A Giulivi A Coulthart M Delasnerie-Laupretre N Brandel JP Zerr I Kretzschmar HA de Pedro-Cuesta J Calero-Lara M Glatzel M Aguzzi A Bishop M Knight R Belay G Will R Mitrova E;EUROCJD 《Human genetics》2005,118(2):166-174
A total of 10–15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt–Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann–Sträussler–Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12–88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt–Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term “gTSE” is preferable to “familial TSE”. Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.Gábor G. Kovács and Maria Propolo Contributed equally 相似文献