Association between haptoglobin groups and hereditary predisposition for bronchial asthma

Haptoglobin (Hp) groups were investigated in 148 patients with bronchial asthma. A significant (p less than 0.005) deviation from the expected Hardy-Weinberg equilibrium, with a decreased frequency of heterozygotes, was observed among patients with a family history of asthma. This deviation was more pronounced among patients with adult onset of asthma. The presence or absence of atopy had no significant influence on the phenotype distribution.     

Genetic factors of predisposition to endometriosis and response to its treatment]

The relative frequencies of the normal (+) and null (0) alleles of the glutathione-S-transferase M1 (GSTM1) gene, as well as those of the rapid (R) and slow (S) forms of N-acetyl transferase 2 (NAT-2), were studied in the Russian and French populations and in endometriosis (EM) patients. In the total Russian and French populations, the proportions of homozygotes for deletion in gene GstM1 (0/0) were 42.2 and 45.8%, respectively, whereas in Russian and French EM patients, these values were 58.6 and 76.9%, respectively. The differences in these proportions between the total population and subjects with EM were significant at the confidence levels of 0.98 (chi 2 = 5.45; P < 0.02) and 0.90 (chi 2 = 3.01; P < 0.1) for the French and Russian populations, respectively. The frequencies of allele S of the Nat-2 gene were also similar in the Russian and French populations (60 and 63.1%, respectively), with these frequencies being somewhat higher in EM patients (71.2 and 77.7%, respectively). In Russians, the proportion of EM patients who were homozygous for the R form of NAT-2 (R/R) was significantly lower (chi 2 = 5.1). Forty-three of the patients with external genital EM received complex treatment with the use of the interferon inducer Cyclopheron. In 17 patients, a pronounced positive dynamics was observed, and 29 patients exhibited an increased resistance to the immunomodulating therapy. These groups comprised 1 and 25 GstM1 0/0 homozygotes, respectively; the number of patients with the slow NAT-2 form was 13 (7 S/S and 6 S/R genotypes) and 29 (20 S/S and 9 S/R genotypes), respectively. The obtained data indicate that the GstM1 and Nat-2 genes are involved in the EM pathogenesis. Therefore, molecular screening for the GstM1 0 and Nat-2 S alleles would be a good prognostic test when prescribing the postoperative treatment for EM and predicting its effectiveness.     

Genetic predisposition to multiple myeloma

Genetic myeloma risk research relied on genome-wide association studies to identify 24 common but lowimpact germline predisposition alleles that account for an estimated one eighth of the heritable myeloma risk in Caucasians. Next-generation sequencing, particularly whole-exome sequencing, uncovered a handful of rare but high-impact myeloma risk loci that convey intriguing clues about etiology. The recent discovery of NCOA1 as a myeloma susceptibility gene in Han Chinese has set the stage for the more complete elucidation of the genetic myeloma risk across ethnic barriers. Validating individual myeloma risk loci at the functional level and integrating predisposition genes in genetic networks and biological pathways are important research tasks going forward. Candidate pathways that are currently emerging include plasma cell development, autophagy, telomere maintenance, and cell cycle regulation. An outstanding knowledge gap in the area of gene-environment interaction concerns the possibility that tumor-promoting effects of myeloma susceptibility alleles depend on specific environmental or occupational exposures. An implicit promise of myeloma risk research is the detection of new molecular targets for myeloma treatments and preventions. A related outcome is new biomarkers for patient stratification, prognostication, and development of individualized treatment plans.     

Genetic predisposition to papillary thyroid cancer

Approximately 5% of differentiated thyroid cancers are hereditary. Hereditary non-medullary thyroid cancer may occur as a minor component of familial cancer syndromes (e.g. familial adenomatous polyposis) or as a primary feature (familial non-medullary thyroid cancer [FNMTC]). Among FNMTC, PTC is the most common. Although a hereditary predisposition to non-medullary thyroid cancer is well established, the susceptibility genes are poorly known. Up to now, by linkage analysis using microsatellite markers, several putative loci have been described - 1q21, 6q22, 8p23.1-p22, and 8q24; however, validation studies have been unsuccessful. In the present review we discuss the results of linkage analysis and the most recent results of genome wide association studies (GWAS) with high resolution SNP (single nucleotide polymorphism) arrays.     

Genetic predisposition to ovarian cancer.

Chronic orthostatic hypotension is caused by a variety of disorders. Frequently patients withdraw from social interactions, are prone to adverse drug reactions and inappropriate diagnoses, and are bed-bound by the time of diagnosis. Applying basic principles of cardiovascular physiology and pharmacology usually permits these patients to lead active lives and to live longer. Much of the management is based on common sense and knowledge of the basic pathophysiology of the disorder and depends on thorough patient education and close monitoring of blood pressure in many of the activities of daily living.     

Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature

Some cases of pancreatic cancer (PC) are described to cluster within families. With the exception of PALLD gene mutations, which explain only a very modest fraction of familial cases, the genetic basis of familial PC is still obscure. Here the literature was reviewed in order to list the known genes, environmental factors, and health conditions associated with PC or involved in the carcinogenesis of the pancreas. Most of the genes listed are responsible for various well-defined cancer syndromes, such as CDKN2A (familial atypical mole-multiple melanoma, FAMMM), the mismatch repair genes (Lynch Syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and BRCA2 (breast–ovarian familial cancer), where PC is part of the cancer spectrum of the disease. In addition, in this review I ranked known/possible risk factors extending the analysis to the hereditary pancreatitis (HP), diabetes, or to specific environmental exposures such as smoking. It appears that these factors contribute strongly to only a small proportion of PC cases. Recent work has revealed new genes somatically mutated in PC, including alterations within the pathways of Wnt/Notch and DNA mismatch repair. These new insights will help to reveal new candidate genes for the susceptibility to this disease and to better ascertain the actual contribution of the familial forms.     

Neurotrophins in bronchial asthma

Allergic bronchial asthma (BA) is characterized by chronic airway inflammation, development of airway hyperreactivity and recurrent reversible airway obstruction. T-helper 2 cells and their products have been shown to play an important role in this process. In contrast, the mechanisms by which immune cells interact with the cells residing in lung and airways, such as neurons, epithelial or smooth muscle cells, still remains uncertain. Sensory and motor neurons innervating the lung exhibit a great degree of functional plasticity in BA defined as 'neuronal plasticity'. These neurons control development of airway hyperresponsiveness and acute inflammatory responses, resulting in the concept of 'neurogenic inflammation'. Such quantitative and/or qualitative changes in neuronal functions are mediated to a great extent by a family of cytokines, the neurotrophins, which in turn are produced by activated immune cells, among others in BA. We have therefore developed the concept that neurotrophins such as nerve growth factor and brain-derived neurotrophic factor link pathogenic events in BA to dysfunctions of the immune and nervous system.     

Genetic predisposition to catatonic behaviour and methylphenidate sensitivity in rats

To study the relationship between three animal models of schizophrenia, i.e. genetically determined akinetic catatonia, stereotypies induced by amphetamine-like psychostimulators, and behavioural changes in chronic intoxication with such stimulators, the frequency of different types of reactions to a functional amphetamine analogue, methylphenidate, was studied in wild Norway rats, non-selected Wistar rats, and Wistar rats bred for predisposition to akinetic catatonia. A positive relationship between the predisposition to catatonia and the level of stereotypies in a single methylphenidate administration was found in wild rats, but not in Wistar bred for catatonia (the latter differed from the non-selected rats in a higher frequency of “hyperactive” reactions). A closer study of catatonia in laboratory rats permitted subdivision into several types—occurring in selected and non-selected rats both naturally and as a result of chronic intoxication with amphetamines. It was found in non-selected Wistar rats that there is a positive relationship between some of these types and an increased stereotypy level in repeated methylphenidate administration. It is concluded that the natural akinetic catatonia and the chronic intoxication with amphetamines are two homologous varieties of the same model of schizophrenia, while the stereotypies are characteristics of this model. Studies of monoamine oxidase (MAO) activity imply a cortical component in the predisposition to akinetic catatonia.     

支气管扩张合并支气管哮喘患者的病原菌检测及危险因素分析

目的分析支气管扩张合并支气管哮喘患者的病原菌及危险因素。方法选取湖州市中心医院115例支气管扩张合并支气管哮喘患者作为观察组,另选取同期110例健康体检者作为对照组。分析患者病原菌的组成、耐药性及发病危险因素。结果观察组患者送检痰样本经痰培养,阳性检出者68例,阳性率为59.13%(68/115)。全部样本共分离出104株病原菌,其中革兰阴性菌92株(以铜绿假单胞菌最多,占54.81%),革兰阳性菌8株,真菌4株。药敏试验结果表明革兰阴性菌对复方新诺明、头孢曲松、左旋左氧氟沙星和阿莫西林/克拉维酸等药物的耐药性均较高,对妥布霉素、亚胺培南、头孢哌酮/舒巴坦和哌拉西林的耐药性较低。Logistic回归分析显示,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎、哮喘、过敏性肺炎、慢性支气管炎及慢性阻塞性肺疾病均是支气管扩张伴支气管哮喘发生的危险因素。结论支气管扩张合并支气管哮喘患者其病原菌以革兰阴性菌为主,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎等是支气管扩张伴支气管哮喘发生的危险因素。     

Genetic predisposition to obesity and risk of subclinical atherosclerosis

Obesity has been associated with increased common carotid artery (CCA) intima–media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (p < 0.001) after adjustment for age and gender. Per 2 alleles of the GRS was related to 0.023 mm increment in IMT. The association was attenuated by one half with additional adjustment for obesity status, but remained significant (p = 0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction = 0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ≥ 120 mm Hg and/or diastolic blood pressure (DBP) ≥ 80 mm Hg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trend < 0.001) than those with SBP < 120 mm Hg and DBP < 80 mm Hg (per 2 allele increment of the GRS relating to 0.001 smaller CCA IMT, p for trend = 0.930). Our data provides suggestive evidence supporting the potential causal relation between obesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk.     

Genetic markers of individual predisposition to lung cancer]

The investigation concerning the dependence of cancer incidence on genetic HLA-markers and character of dermatoglyphs was carried out. The use of the pattern recognition method for multifactorial estimation of the above markers as well as the elimination of the main non-genetic oncogenic risk factors allowed obtaining the proof of the existence of the genetic predisposition to lung cancer. It was estimated that the character of dermatoglyphic prints is the most adequate marker for the investigated predisposition, and the reliable prediction of the genetic risk of the lung cancer development can be given as based on the joint evaluation of both markers.     

Genetic predisposition to cancer - insights from population genetics

Individuals differ in their inherited tendency to develop cancer. Major single-gene defects that cause early cancer onset have been known for many years from their inheritance patterns, and inherited defects that have weaker effects on predisposition were also suspected to exist. Recent progress in cancer genetics has identified specific loci that are involved in cancer progression, many of which have key roles in DNA repair, cell-cycle control and cell-death pathways. Those loci, which are often mutated somatically during cancer progression, sometimes also contain inherited mutations. Recent genetic studies and quantitative population-genetic analyses provide a framework for understanding the frequency of inherited mutations and the consequences of these mutations for increased predisposition to cancer.