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CNAA / Theses / 2009 / June /

The clinical and evolutional peculiarities of the mixed connective tissue disease and the reveling of some genetic markers

Author: Lupaşcu-Volentir Felicia
Degree:doctor of medicine
Speciality: 14.00.06 - Cardiology and Reumatology
Scientific adviser: Liliana Groppa
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific consultant: Nicolae Barbacar
doctor habilitat, professor, Institute of Genetics, Physiology and Plant Protection of the ASM
Scientific council:


The thesis was presented on the 25 June, 2009
Approved by NCAA on the 1 October, 2009


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the mixed connective tissue disease, the clinic manifestations, the polymorphism, the genetic markers, the interleukins


The clinical and evolutional peculiarities of the mixed connective tissue disease (MCTD) and its genetic markers are reveled in this thesis. The study included 125 women with Connective Disease Tissue (CTD): 50 patients were from the main group and 75 patients - from the control groups (25 patients – with SLE, 25 patients – with SS, 25 patients – RA). The patients passed a complex, carefully examination to determine the joint and extra-joint injury degree. The studied groups were compared by the patient age at the onset and the present manifestations of the disease and by it’s evolution. In this way, for the main group, the mean age at the onset of the disease was 31,5±1,6 years, at the examination – 48,7±1,7 years and the mean period of the disease evolution was 17,3±1,2 years. The first clinical manifestations of the MCTD were the diffuse joint pain and the arthritis. During the examination the joint manifestation frequency of the MCTD was less expressed in comparison with RA (maximum incidence) and has a higher percentage than in SS and SLE (minimum incidence). In comparison with the control groups the patients with MCTD showed more frequently the hip joint pains and a large variation of the extra-joint signs. The monophasic character of the Raynaud syndrome with different complications (the finger pulp ulcerations, the cicatrices and the high level of CRP) predominated in the patients with MCTD. The different organs/systems are the components of the MCTD. A pronounced clinic polymorphism was determined by the multidimensional squalling of the patients from the studied groups according to the join and extra-joint signs of the diseases. The correlation and regression analyses showed the important divergences between the different clinical indices with the predictive value. By the factorial analysis it was determined that the clinical injures can be classified into the specific and non-specific manifestations of the MCTD type common for the CTD. By the cluster analysis (k-mean method) the relevant indices (as phenotypic markers of the MCTD) and the associative dependency of the clinical signs were reveled. By the DNA polymorphism analysis (the PCR method) for the genes which control the cytokine IL 1, IL 6, CTLA 4 synthesis and by the cluster analysis it was determined that the study group with MCTD is rather genetic polymorph and show the different associations of the abnormal alleles for the IL 1, IL 6 and CTLA 4 genes. This genetic polymorphism is the origin of MCTD, so it can be named the clinic polymorphism of the disease. As a result of the clinical manifestations study and of the functional organic indices examination; the study of the DNA polymorphism for the genes which control the IL 1, IL 6 cytokines and CTLA 4 synthesis; the application of the modern informational statistic technologies, the existence of the MCTD as a distinct pathology was confirmed. The opportunity of the DNA molecular markers of the mentioned above cytokines utilization in order to predict the type of MCTD clinic manifestation was proved. This fact will contribute mainly to the elaboration of the system-support decision in the program of the diagnostic and therapeutic strategy of this disease.