Введение Исследования последних лет расширили представления о сосудистом эндотелии как об анатомическом образовании, и с позиции современной фундаментальной медицины эндотелий рассматривается как активная метаболическая система, поддерживающая сосудистый гомеостаз путем осуществления разнообразных функций (модуляция сосудистого тонуса, регуляция хемотаксических, репаративных и воспалительных процессов в ответ на локальное повреждение, формирование внеклеточного матрикса) [1]. Данные функции эндотелий осуществляет путем сбалансированного синтеза и выделения ряда биологически активных соедине
Our aimwas to study the influence of IL4-589C>T gene polymorphism on IL-4 expression in patients, living in Zabaikalsky Region with a diagnosis of chronic traumatic osteomyelitis developing after fractures of long bones of extremities.The study included 132 patients with fractures of long bones at the age of 20 to 40 years old. The first group consisted of 83 patients with uncomplicated course of fractures; the second group (n = 49) included patients with chronic traumatic osteomyelitis healed by primary wound closure, however, developing chronic traumatic osteomyelitis over late postoperative period. The control group consisted of 100 practically healthy men and women of the same age group. These groups were homogeneous and similar by age, sex, origin and localization of fractures. Presence of acute or chronic comorbidities was the exclusion criterion. We applied clinical examination, instrumental tests (X-ray studies), laboratory methods (microbiological, immunological, ELISA for IL-4 measurement). IL-4 point mutation at position 589 (C>T) was tested by PCR; the DNA for this analysis was extracted from peripheral blood. The genetic studies were performed when patients entered the hospital. IL-4 contents, clinical and instrumental indicators were detected on 1, 2, 10 and 90 days after fracture. Resultsof the study were as follows: the frequency of the C allele and the homozygous genotype of the IL4- 589C>T gene in the patients with complicated clinical course was decreased 1.7- and 3.6-fold compared with the comparison clinical group, respectively. Frequency of T allele, by contrast, increased 3.7-fold, whereas heterozygous and mutant genotypes were changed 2.5 and 15 times against the comparison group. The persons from control group with IL4-589C/C genotype, showed a 1.4- and 2.5-fld increased IL-4 concentration as compared with the carriers of the -589C/T and -589T/T genotypes, respectively, and in -589C C/T genotype, 1.7-fold compared to -589Т/T genotype. A similar trend of IL-4 expression, depending on the IL4 genotype, was recorded in the group with both uncomplicated and complicated course of fractures. In conclusion, the patients with developing traumatic osteomyelitis showed ncreased frequency of the IL4 -589T allele (3.7-fold as compared with uncomplicated group). Meanwhile, higher frequency of the -589C/T -589T/T genotypes of the IL4 gene were registered. Genotype -589T/T of the IL4 gene is associated with lower IL-4 expression.
Цель. Выявление персонифицированных диагностических критериев нарушений консолидации при переломах костей конечностей. Материалы и методы. В исследование включено 108 пациентов в возрасте от 20 до 40 лет (по ВОЗ) с переломами костей конечностей. Первая группа -62 пациента с неосложнённым течением переломов. Вторая (n = 46) -пациенты с нарушением консолидации. Критерием исключения из групп являлось наличие острых или хронических сопутствующих заболеваний. Данные клинического, лабораторного и инструментального методов определялись при поступлении в стационар, затем на 2, 5, 10 и 90 сутки исследования (210 показателей) и оценивались в многомерной прогностической регрессионной модели. Статистическая обработка выполнялась с помощью пакета программ STATISTICA 6.1 (StatSoft, Russia). Результаты. Используемый многомерный регрессионный анализ выявил высокую связь генотипа -25Pro/Pro гена TGFβ 1 и генотипа -2073Т/T гена EGFR-2073A > T у пациентов с нарушением консолидации по типу замедленной консолидации (p < 0,0000001). Заключение. В качестве одного из маркеров нарушения консолидации переломов костей конечностей может использоваться сочетание генотипов -25Pro/Pro гена TGFβ 1 и -2073Т/T гена EGFR, что позволит использовать персонифицированную профилактическую программу для предотвращения данной группы осложнений. Ключевые слова: переломы, нарушение консолидации, полиморфизм, гены, прогноз Purpose Identification of personalized diagnostic criteria of consolidation disorders in limb bone fractures. Materials and methods 108 patients at the age from 20 to 40 years (according to WHO classification) with limb bone fractures were included into the study. Group 1 were patients (n = 62) with uncomplicated fractures. Group 2 (n = 46) included patients with consolidation disorders. The presence of acute or chronic associated diseases was the exclusion criteria. Clinical, laboratory and instrumentation findings (210 parameters) were assessed in a multivariate predictive regression model. These parameters were studied at admission, then on days 2, 5, 10 and 90 of the study. Statistic processing was performed using STATISTICA 6.1 software package (StatSoft, Russia). Results The multivariate regression analysis used revealed high association of -25Pro/Pro genotype of TGFβ 1 gene and -2073Т/T genotype of EGFR-2073A > T gene in patients with consolidation disorders that ran as delayed consolidation type (p < 0.0000001). Conclusion The combination of genotypes -25Pro/Pro of TGFβ 1 gene and -2073Т/T of EGFR gene can be used as one of the markers of consolidation disorder in limb bone fractures, and that will enable to use personalized prophylactic programs to prevent such complications.
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