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Background: Hallux valgus (HV) is a type of forefoot deformity affecting ∼23% of adults. Previous studies have shown that HV is highly heritable. Tumor necrosis factor (TNF) is an important proinfl...

Исследование проводили для определения генетической структуры популяции казахской белоголовой породы крупного рогатого скота по генам-маркерам липидного обмена лептина (LEP), к-казеина (CSN3), бета-лактоглобулина (BLG), тиреоглобу-лина (TG5), а также фактора некроза опухоли (TNF-a) и выявления их связи с энергией роста молодняка. ДНК-типирование 202 коров осуществляли в 2017 г Генное равновесие в стаде по всем генам не нарушено. Уровень гомозиготности в популяционной выборке животных находился в пределах от 50 % (LEP) до 68 % (TG5). По генам CSN3 и BLG частота аллеля А составила 0,74 и 0,40, аллеля В - 0,26 и 0,60 соответственно. По генам LEP и TG5 частоты аллелей C были равны 0,52 и 0,80 соответственно; Т- 0,48 и 0,20. По гену TNF-a частота аллеля А составила 0,33, аллеля G - 0,67. Ассоциативные связи между генотипами и энергией роста молодняка в течение года после рождения незначительны. У телят с генотипом LEP17, в сравнении со сверстниками с генотипом LEP01, среднесуточный прирост в 9- и 10-месячном возрасте был выше на 166 и 138 г соответственно. Более высокая энергия роста за первый месяц отмечена у телят с генотипом TG5СС - на 124 г больше, чем у животных с TG5CT. По другим генотипам и в другие периоды роста различия между генотипами по среднесуточному приросту были недостоверными. Результаты молекулярно-генетического анализа казахской белоголовой породы целесообразно использовать при разработке планов селекционно-племенной работы в стадах с целью эффективного отбора и подбора родителей.The purpose of the study was to determine the genetic structure of the Kazakh white-headed cattle population by the marker genes of lipid metabolism of leptin (LEP), kappa-casein (CSN3), beta-lactoglobulin (BLG), thyroglobulin (TG5), as well as tumor necrosis factor (TNF-alpha) and to identify their relationship with the growing energy of young animals. DNA typing of 202 cows was conducted in 2017. The herd was genetically balanced. The homozygosity level in the population sample of animals ranged from 50% (LEP) to 68% (TG5). For CSN3 and BLG, the frequency of allele A was 0.74 and 0.40, whereas the frequency of allele B was 0.26 and 0.60, respectively. For LEP and TG5, the frequencies of alleles C were 0.52 and 0.80, respectively; the frequencies of alleles T were 0.48 and 0.20, respectively. In gene TNF-alpha, the frequency of allele A was 0.33; the frequency of allele G was 0.67. Associative relations between genotypes and growth energy of young animals during the first year after birth were insignificant. In calves with genotype LEP(TT), in comparison with peers with genotype LEP(cC), the average daily increase at 9 and 10 months was higher by166 g and 138 g, respectively. Higher growth energy for the first month was observed in the calves with genotype TG5(CC) - 124 g more than in the animals with genotype TG5(CT). For other genotypes and in other periods of growth, differences between the genotypes in daily average growth were insignificant. It is advisable to use the results of the molecular genetic analysis of the Kazakh white-headed cattle when planning breeding in herds in order to effectively select parents.

Обоснование: В настоящее время анализ генетической предрасположенности к развитию инфаркта миокарда (ИМ) у больных трудоспособного возраста является предметом актуального научного поиска. Цель исследования: изучить возможную ассоциацию риска развития ИМ с полиморфным вариантом G(–308)А гена TNF у больных младше 60 лет. Методы: В простое открытое сравнительное исследование по типу «случай-контроль» в период с 01.10.2018 по 30.06.2019 г. было включено 150 больных (124 мужчины и 26 женщин) в возрасте младше 60 лет (медиана возраста 49,57 лет). Основную группу пациентов (больные ИМ) составили 95 человек (78 мужчин и 17 женщин), госпитализированных в один из региональных сосудистых центров г. Перми в первые сутки от момента развития клинической симптоматики. Группу сравнения, сопоставимую с основной по возрасту и половой структуре, составили 55 человек. Для oпрeдeлeния oднoнуклeoтидных пoлимopфизмoв прoвoдили aллeль-спeцифичeскую пoлимepaзную цeпную peaкцию нa aмплификaтope «CFХ-96» Bio-Rad Laboratories, Inc. (СШA) с дeтeкциeй прoдуктoв в рeжимe рeaльнoгoврeмeни. Для выдeлeния ДНК испoльзoвaли нaбoры рeaгeнтoв «К-Сoрб» (OOO «Синтoл», г. Мoсквa). Статистический анализ проводился с помощью пакета сертифицированных компьютерных программ SPSS Statistics. Для оценки ассоциации аллелей и генотипов с риском развития ИМ вычисляли отношение шансов (ОШ) и 95%-й доверительный интервал (ДИ). Результаты: Определено, что генотип GG преобладал в группе сравнения. В основной группе, напротив, генотип GG регистрировался реже (80,0% против 60%, ОШ = 0,38; 95% ДИ: 0,17 – 0,82, p=0,030) за счёт статистически значимого увеличения доли аллеля А. Для генотипов GA+AA вероятность развития ИМ возрастала более чем в 2,5 раза (c2 = 6,33, ОШ=2,67 (95% ДИ:1,23-5,8), p=0,012). Заключение: Полученные результаты позволяют предположить, что развитие ИМ у больных трудоспособного возраста имеет генетическую детерминированность и ассоциировано с носительством аллеля A полиморфного маркера G–308A гена TNF. Генетический полиморфизм rs 1800629 гена TNF определяет вероятность преждевременного развития ИМ вне зависимости от наличия традиционных факторов риска., Background: At present, the analysis of the genetic predisposition to the development of myocardial infarction (MI) in patients under 60 years old is the subject of an urgent scientific search. Aims: To study the relationship of G308A polymorphic variants of the tumor necrosis factor (TNF) gene with the risk of acute myocardial infarction (MI) in young and middle-aged patients. Materials and methods: The study included 95 patients with MI (78 males and 17 females) of a Caucasoid race aged ≤60 years (49,0 (38,0–50,0) and 55 patients without coronary heart disease. Patients from both groups were comparable in terms of sex,age, and examined factors of cardiovascular diseases risks. The rs 1800629 polymorphism of TNF gene (G308A) was tested using real-time polymerase chain reaction (CFХ-96, Bio-Rad Laboratories, Inc., USA) with test-systems produced by “Sintol” LLC (Moscow). To assess relations between alleles and genotypes and disease risks, we calculated odds ratio (OR) with 95 % confidence interval (CI). Results: In the assessed groups, the frequency of alleles and gene TNF genotypes was measured: 2 patients carried genotype АА (1,4%), 47 patients — GA (31,3%), 101 — GG (67,3%). It was determined that the GG genotype prevailed in the comparison group (patients without coronary heart disease). In the main group (patients with MI), on the contrary, the GG genotype was recorded less frequently (80.0% versus 60%, OR = 0.38; 95% CI: 0.17 - 0.82, p = 0.030) due to a statistically significant increase in the share of the A. For GA + AA genotypes, the probability of developing MI increased by more than 2.5 times (c2 = 6.33, OR = 2.67 (95% CI: 1.23-5.8), p = 0.012). Conclusions: Carriage of the rare A allele of polymorphic marker G(-308)A gene TNF is associated with more common development of MI in young and middle-aged patients., Уральский Медицинский Журнал, Выпуск 10 2020

AIM To investigate genetic factors that might help define which Crohn’s disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy. METHODS This was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria). RESULTS 121 patients were included. Twenty-one were non-responders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs. CONCLUSION The Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.

Tumor necrosis factor (TNF) has been shown to be involved in the pathogenesis of hemorrhagic stroke, having deleterious effects on cerebral arteries by promoting inflammation and apoptosis in vascular and immune cells. In this study, we investigated genetic association between TNF gene and intracerebral hemorrhage (ICH) in a Korean population.Single nucleotide polymorphisms (SNPs) of TNF gene [-857C/T (rs1799724) and -308G/A (rs1800629)] were selected and genotyped using direct sequencing in 144 ICH patients and 455 control subjects. Genotype distribution and allele frequency were compared between cases and controls using logistic regression.-857C/T was significantly associated with ICH in log-additive [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.14-2.24, p = 0.0081], and recessive models (OR = 3.25, 95% CI = 1.28-8.27, p = 0.016). The frequency of the -857TT genotype increased in ICH patients. Allele frequency analysis also showed that the -857T allele was associated with an increased risk of ICH (OR = 1.62, 95% CI = 1.15-2.30, p = 0.006). In the analysis according to the gender, we found that the association of -857C/T was gender-different. The -857C/T was significantly associated with ICH only in males (OR = 1.99, 95% CI = 1.24-3.19, p = 0.0043 in males; OR = 1.30, 95% CI = 0.76-2.22, p = 0.34 in females).These results suggest that promoter polymorphism of TNF gene, -857C/T, may be involved in the susceptibility of ICH in males.

Analysis of microsatellite TNFalpha marker and (-308(G/A) polymorphisms in promoter of TNFalpha gene was conducted in 167 patients with various types of sporadic breast cancer (BC) as well as in 139 healthy Russian donors. It was shown that frequency of allele 7 in TNFalpha microsatellite marker was significantly higher in BC patients than in healthy donors (17.9% versus 10.4%; P = 0.02) mainly due to the patients with invasive ductal BC (19.2% versus 10.4%; P = 0.008). The TNFalpha allele 9 was observed significantly more frequently in patients with invasive-ductal cancer (6.4% versus 1%; P= 0.01). The studies of-308(G/A)TNFalpha polymorphism in BC patients and healthy donors have shown no differences in the distribution frequency of highly secreted allele (-308A)TNFalpha. However, invasive lobular BC patients carrying (-308AG)TNFalpha genotype were observed significantly more frequently than invasive-ductal BC patients carrying the same allele (34.0 versus 17.3%; P = 0.034). Thus it has been shown for the first time that invasive-ductal and invasive-lobular BC patients differ in distribution of TNFalpha and -308(G/A)TNFalpha alleles.

This study evaluates tumor necrosis factor (TNF)-alfa gene expression in patients with end-stage renal disease (ESRD) on regular hemodialysis as an expression of cardiovascular disease (CVD) risk even on a sub-clinical level and its relation to some of the parameters incriminated in the pathogenesis and the establishment of uremic arteriopathy. A total of 51 patients with ESRD on regular hemodialysis and 20 healthy subjects matching in age and gender as a control group were recruited. All selected cases were subjected to serum lipid profile, Creactive protein (CRP), TNF-alfa gene expression and Doppler study of carotid arteries to estimate carotid intimal media thickness (cIMT). Serum triglycerides (TGS) level (P

To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF-alpha concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU).A total of 112 postoperative critically ill infected patients were prospectively enrolled.SICU of a tertiary university-affiliated medical center.Patients who were consecutively admitted to the SICU because of surgical infection with sepsis.Blood sampling.Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the TNF-alpha.The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p.05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels.In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-alpha level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

Sickle cell disease is a common worldwide disorder that can lead to stroke in affected individuals. This chapter describes the epidemiology, pathophysiology, and genetics that contribute to the onset of this disorder. Evidence-based treatment recommendations are also given.

BACKGROUND AND PURPOSE Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-β gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-β gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-β gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS Forty-seven migraine patients (6 males and 41 females; age 36.4±10.3 years, mean±SD) and 22 MOH patients (1 male and 21 females; age 39.6±9.9 years) who had migraine were included in this study. The genotype for the TNF-β gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS The distribution of TNF-β gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients. CONCLUSIONS G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-β gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.

The immune response to injury involves a complex pattern of primary, secondary and tertiary humoral and cellular responses. Genetic variability in the expression of the mediators comprising these responses constitutes the genetic background which may potentially influence the course of inflammation in each individual. Differences in this background may in part explain the highly variable clinical courses noted among septic patients. Comparable doses of infecting microbes may induce a wide range of severity of illness due in part to genetic variability.

Heat shock protein (HSP) and endogenous tumor necrosis factor (enTNF) both act as resistance factors against the cytotoxicity of various cellular stresses. To clarify the relationship between these two stress response systems, we investigated whether or not enTNF is capable of inducing HSP72. Without heating, no difference was found in HSP72 synthesis between enTNF-nonexpressing L-M cells and cells expressing L-R or L-M (pcDV-TNF). After initiation of heat treatment, however, a remarkable increase in HSP72 synthesis was noted in enTNF-expressing cells compared to enTNF-nonexpressing L-M cells. These findings indicated that enTNF augments heat-inducible HSP72 synthesis.

We have recently learned many lessons regarding the role of hematopoieti-cally derived cells, and the marcophage in particular, in the etiology of gram-negative septic shock. Perhaps the most important lesson, and the lesson which still invites the most avid experimentation, was that taught by the C3H/HeJ mouse. These animals carry a genetic defect, localized to the 4th chromosome [1], which deprives them of the ability to respond to lipopoly-saccharide (LPS). As a result, the mice can sustain the injection of enormous quantities of LPS; the dose-lethality curve for this strain is shifted “downfield” by a factor of 100 or more [2]. Indeed, it is not clear that the animals ever succumb to the injection of highly purified LPS preparations.

To investigate TNF-alpha-308 and TNFB polymorphisms in acute biliary pancreatitis (ABP) and to related them to the plasma TNF-alpha levels.Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients (n=127) and healthy controls (n=102) using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Reading the size of digested bands from polyacrylamide gel demonstrated the two alleles TNF1 and TNF2, or the two alleles TNFB1 and TNFB2.The frequencies of TNF2 polymorphism and TNFB2 polymorphism were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. Patients with septic shock showed a significantly higher prevalence of the TNF2 than those without. No significant differences were found in the genotype distribution of TNF-alpha-308 and TNFB among different groups. Plasma TNF-alpha levels did not differ significantly in ASBP patients displaying different alleles of the TNF gene studied.Results indicate that TNF gene polymorphisms studied play no part in determination of disease severity or susceptibility to acute biliary pancreatitis; however, TNF2 polymorphism is associated with septic shock from ASBP. Genetic factors are not important in determining plasma TNF-alpha levels in ASBP.

2002;121;87S-88S Chest William Y. Park, C. W. Frevert, V. A. Wong and T. R. Martin * Phenotypes in 101 Normal Human Subjects High and Low Inflammatory Response http://chestjournal.chestpubs.org/content/121/3_suppl/87S.2.full.html can be found online on the World Wide Web at: The online version of this article, along with updated information and services ) ISSN:0012-3692 http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( distributed without the prior written permission of the copyright holder. All rights reserved. No part of this article or PDF may be reproduced or College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. has been published monthly since 1935. Copyright2002by the American is the official journal of the American College of Chest Physicians. It Chest

87(41%), circumflex in 69(32%), and the RCA in 57(27%). Follow-up angios to determine the need for re-intervention were usually obtained at 3 and 6 mos, then yearly. Repeat PTCA was routinely applied to vessel sites with 60% re-stenosis. Results: PTCA was successful in reducing the site of stenosis to 20% in 165 of 190(87%) procedures. Subsequent repeat PTCA occurred in 69 of 214 vessels (32%), with no difference according to vessel (p .1). PTCA procedure-related mortality was 2% (4/157). The actuarial freedom from re-PTCA (of same vessel site) was 77% at 6mo, 66% at 1 yr, and 60% at 4 yrs. The freedom from re-PTCA after a repeat PTCA was 53% at 1 yr (p .0003 compared to initial PTCA). By univariate analysis, the freedom from re-PTCA was associated with the use of stents (27% re-PTCA at 1 yr with stents vs 38% without, p .03). However, by multivariate analysis, an era effect neutralized the impact of stenting: re-PTCA during era 1 (1990 to1997) was 43% at 1 yr vs 21% during era 2 (1997 to 2001), (p .0004). In the setting of 1-vessel disease at first PTCA the 2 yr freedom for CAV death or graft loss was 74%, compared to 75% for 2-vessel and 27% for 3-vessel disease (p .009). Inferences: 1) PTCA is effective palliation for CAV, with rePTCA rate 30% at 3 yrs in current era. 2) Stents appear to increase effectiveness of PTCA for CAV. Other factors in the current era contribute to improved outcome. 3) Despite the increasing effectiveness of PTCA for localized CAV, the survival after development of advanced CAV remains poor, indicating the need for additional treatment strategies for these pts.