CC BY
26
After 12 months from the surgery the patient walks without assistance, motions in right hip joint are in full. Flexion in the hip joint is 90°, extension is 180°, abduction and adduction are 15°, all movements are painless. Long distance walks do not require additional support.
Evaluation of functional state ofhip j oint after surgery was 10 points. Evaluation of functional state of hip joint is qualified as good. This patient is to have the left hip replacement for full satisfaction oftreatment.
Thus rheumatoid coxitis depending on clinical signs has four stages, and also characteristics of pain, limiting of flexion, exten-
sion, abduction and adduction, reduction of hip muscles force with changes of rising from "semi-erect" position and rising/sitting down, walking speed and decreasing of daily life activity.
Conclusions:
1. Clinical symptoms of rheumatoid coxitis have 4 stages.
2. Severity of clinical signs depends from stage of disease.
3. Rheumatoid coxitis of stage III and IV leads to profound disability and becomes an indication to the replacement of the hip.
References:
1. Marinus D. J. Stowers, Daniel P Lemanu, Brendan Coleman, Andrew G Hill, Jacob T Munro (2014) Review Article: Perioperative care in enhanced recovery for total hip and knee arthroplasty. Journal of Orthopaedic Surgery - 2014; - 22 (3):383-92.
2. Svege Ida, Nordsletten Lars, Fernandes Linda, May Arna Risberg (2015) Extended report: Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised trial. Ann Rheum Dis - 2015; - 74:1; - 164-169.
3. Peter W. F., Tilbury C., Tordoir R., Verdegaal S. H., Onstenk R., Benard M., Vehmeijer S. B., Van der Linden-Zwaag E. M., Nelissen R. G., VlietVlieland T. P. (2013) Preoperative physical therapy in total hip and knee replacement surgery: a multi center study. Ann Rheum Dis - 2013; 72: Suppl 3 A 578.
4. Hoeksma H. L., Van den Ende C H M, Ronday H. K., Heering A., Breedveld F. C., Dekker J. (2003) Comparison of the responsiveness of the Harris Hip Score with generic measures for hipfunction in osteoarthritis of the hip. Ann Rheum Dis - 2003; - 62:10; - 935-938.
5. Pisters M. F., Veenhof C., Schellevis F. G., et al. (2010) Long-term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized controlled trial comparing two different physical therapy interventions. Osteoarthritis Cartilage - 2010; -18:1019-26.
6. Beumer L., Wong J., Warden S. J., Kemp J. L., Foster P., Crossley K. M. (2016) Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis. British Journal Sports. Med. - April 1, - 2016. - 50 (8); - 458-463,
7. Dasgupta B., Hutchings A., Hollywood J., et al. (2006) Clinical outcomes, quality of life and diagnostic uncertainty in the first year in polymyalgia rheumatica: a prospective cohort study. Rheumatology - 2006; - 45 (Suppl 1): i170.
8. Bilsel N. et al. (2008) Long-term results of total hip arthroplasty in patients with juvenile rheumatoid arthritis. Acta Orthop. Traumatol. Turc. - 2008. - Vol. 42 (Suppl. 2). - P. 119-124.
9. Heiberg K.E,. (2015) Exercise, Recovery of Physical Functioning, and Prediction of Physical Activity After Total Hip Ar-throplasty. 5-Year Follow-Up of a RCT. Annals of the Rheumatic Diseases, - 2015. - Vol. 74 issue 2. - P. 1318-1319.
10. Leichtenberg C., et al. (2015). Determinants of Returning to Work 12 Months After Total Joint Surgery: Differences Between Total Hip Arthroplasty and Total Knee Arthroplasty/C. Leichtenberg et al.//Annals of the Rheumatic Diseases, - 2015. - Vol. 74. issue 2. - P. 1182-1183.
DOI: http://dx.doi.org/10.20534/ESR-16-11.12-40-43
Ashirmatova Hatira Seidrahimovna, Senior researcher, Department o f eye diseases, Tashkent Medical Academy, E-mail: [email protected] Karimova Muyassar Hamitovna, Tashkent Medical Academy, Department of eye diseases, Professor, Doctor of Medical Sciences, E-mail: [email protected] Boboev Kadirjon Tuhtabaevich, Head of Medical Genetics Laboratory, Institute of Heamatology and Blood Transfusion, Doctor of Medical Sciences, E-mail: [email protected]
Genetic polymorphism of coagulation factors in patients with retinal vein thrombosis
Abstract: The frequency of genetic polymorphism of coagulation factors in patients with retinal vein thrombosis was investigated.) The study revealed the prevalence of homozygous genotype "T677T MTHFR gene" in the main group of patients and higher rate of incidence in men than in women.
Keywords: genetic polymorphism, allele, genotype, retinal vein thrombosis.
Relevance. Thrombosis ofretinal veins represent about 60% of all acute vascular pathology of the eye, are in second place after severity of diabetic retinopathy by retinal lesions and prognosis [1; 2].
Among the risk factors for retinal vein thrombosis, are the most important changes of hemodynamic and hemo-rheological factors: local damage to the vascular wall, leading to the changes of the local coagulation potential; hereditary and acquired disorders in a variety of hemostasis [3; 4].
The issues of homeostasis are attractive for researchers, in order to detect risk factors of thrombosis. Normally, platelets circulate in the blood in an inactive state, and their interaction with intact endothelium lining the blood vessels is quite limited. Only damage to the vessel wall triggers a cascade of processes leading to the formation of a blood clot from platelets and fibrin. However, there are situations where the platelets exert their activity in the bloodstream without a stimulus. This causes an increased risk of thrombosis — platelet thrombophilia.
Depending on pathology of hemostasis components, promoting thrombosis, there are three types of thrombophilia: platelet, vascular and plasma [5; 6; 7]. Verification of the type of thrombophilia is extremely important to optimize the therapy.
According to above stated, there is an urgent need to study the pathogenesis of thrombotic disorders, the development and introduction of molecular methods to identify the genetic disorders, and evaluate the role of genetic markers in predicting the development of retinal vein thrombosis. This will improve the patient examination protocol and adequately verify the risk of progressing the disease, select rational preventive therapy, which in turn contributes to the prevention of severe ophthalmic conditions leading to visual impairment and blindness.
The purpose of research — to study the features of the distribution of alleles and genotypes of polymorphism G20210A prothrombin gene, the FV gene (G1691A) and methyltetrahydrofolat-Table 1
ereductase gene (MTHFR) (C677T) in patients with retinal vein thrombosis.
Materials and methods. The frequency of genetic polymorphisms, associated with thrombophilia, was studied among the local population.
The study included 152 patients with central retinal vein thrombosis and its branches, there were -83men (54.6%), women — 69 (45.4%) aged from 35 to 80 years old. The average age of patients was 61.2 years±2.4 years. Thrombosis of the central retinal vein (CRVO) was observed in74 (48.7%) patients and thrombosis (oc-clussion) of its branches (BRVO) — at 78 (51.3%) patients. Ischemic type of CRVO and its branches thrombosis occurred in 59.2% of cases, non-ischemic type- in 62 patients. The control group included 156 healthy individuals who had no eye disease without thrombotic history.
All the investigated individuals have passed the standard ophthalmic methods of examination.
In addition, as genetic markers of thrombophilia evaluated G1691A mutation in Factor V clotting (V Leiden Factor), G20210A protrotrombina gene, C677T gene in MTHFR. We used the method of polymerase chain reaction with carrying out restriction analysis of amplified DNA segments. The study of genetic markers was conducted in a group ofpatients (152) and the control group (156 apparently healthy individuals), matched by sex and age. The study of group members hipper formed by using monoclonal antibodies with standard methods.
The results were processed using statistical software for Windows — STATISTICA (version 10). For calculations the package of the application programs "Open Epi 2009, Version 2.3" is used.
Results and discussion. As a result of research to 156 donors one man was found to have quite low mutation frequency (G20210 A) FII gene (0.6%), indicating a low incidence of this
marker in the local population. The distribution of alleles and genotypes of polymorphism FII among patients with retinal vein thrombosis and control group
Groups n Allele frequency Frequency of genotype distribution
G A G/G G/A А/А
% % n % n % n %
Main group 152 99 1 149 98 3 2 0 0
Men 83 99,4 0,6 82 98,8 2 1,3 0 0
Women 69 99,3 0,7 68 98,6 1 0,7 0 0
Control 156 99,7 0,3 155 99,4 1 0,6 0 0
Men 79 99,7 0,3 78 99,4 1 0,6 0 0
Women 77 49,4 0 77 49,4 0 0 0 0
In the main group among 152 patients with a mutant allele of blood coagulation FII was detected in three cases (2%). The frequency of mutant alleles of the polymorphism studied in patients and healthy donors was 1% and 0.3%, respectively (X2 = 0.4, P = 0.5; OR = 2.1; 95% CI 0,1867-23, 18). The chance of thrombosis in carriers of this allele in the main group was 2.1 times higher than the control group. At the same time, the distribution of the frequency of heterozygous carriers among the patients and the control group was 2% and 0.6%, respectively. Homozygous genotype of this polymorphism was not detected in both groups.
Assessment of features of the distribution of genotypes and allelic variants of the G20210A prothrombin gene in patients with retinal vein thrombosis according to gender demonstrated that the risk of thrombosis in carriers of the men was higher than that of females (X2 = 0.02; P = 0, 2; OR = 0.8; 95% CI 0,1867-23,18). It must be emphasized that the chance of developing retinal thrombosis among men was slightly higher, but this difference was not statistically significant.
Out of all examined 156 apparently healthy donors, mutant allele — Leiden factor gene was detected in 5 cases (3.2%), carriage of this gene was only heterozygous mutations and homozygous mutations was not detected in the study group.
Out of the surveyed 152 patients with retinal vein thrombosis 8 patients were carriers of mutant alleles in the gene 1691A factor FV clotting in heterozygous state (5.3%), which corresponded to 1.7 fold increase the risk ofvenous thrombosis (p> 0,05, OR = 1.7) compared with the control group (3.2%).
The frequency of mutant 1691A allele of factor V Leiden in the patients examined by gender, men and women, was respectively 2.4% and 2.9%. Among women the presence of FV genotype G1691A genotype detected in 5.8% of cases, and in the group of male patients — 4.8%. Comparative analysis of the prevalence of alleles and genotypes according to gender among patients with retinal vein thrombosis did not reveal much difference of FV (G1691A) polymorphism.
Table 2. - Distribution of allele and genotype polymorphism of G1691A of FV gene in patients with retinal vein thrombosis and control groups
Groups n Allele frequency Frequency of genotype distribution
G A A/A G/A G/G
% % n % n % n %
Main group 152 2,7 97,3 144 94.7 8 5,3 0 0
Men 83 1,4 57,7 79 52% 4 2,75 0 0
Women 69 1,3 39,6 65 42,7 4 2,75 0 0
Control 156 1,6 8,4 151 96,8 5 3,2 0 0
Men 79 0,9 49,7 76 48,7 3 1,9 0 0
Women 77 0,7 48,7 75 48,1 2 1,3 0 0
Table 3. - Distribution of allele and genotype of MTHFR polymorphism among patients with retinal vein thrombosis and control group
Allele frequency Frequency of genotype distribution
Groups n С Т
% % n % n % n %
Main group 152 79,6 20,4 100 65,8 42 27,6 10 6,6
Men 83 76.0 24.0 52 62,7 22 26,5 9 10,8
Women 69 84,1 15,9 48 69,6 20 29.0 1 1,4
Control 156 88,8 11,2 124 79,5 29 18,6 3 1,9
Men 79 86,7 13,3 59 74,7 19 24.0 1 1,3
Women 77 90,9 9,1 65 84,4 10 13 2 2,6
Methyltetrahydrofolatereductase gene mutation (MTHFR) (C677T) was the most frequently identified, both among patients and among healthy individuals. Thus, among the surveyed152, 42 persons were found carriers of mutation C677T MTHFR gene. Distribution of 677T and 677C allele in the control group (156) correspond to the numbers of 0.8 (79.6%) and 0.2 (20.4%), respectively. The overall incidence of C677T MTHFR gene mutation incidence among the control group was 0.32 (32%). 29.0% of them were heterozygous and only 3.0% homozygous genotype.
The frequency of mutant allele carriers 677T (hetero and homozygous) in the total group of patients is 34.2%. According to calculated chances of ratio coefficientcorresponded to more than two times (P <0.05; OR = 2.1).
Comparative analysis of the distribution of genotypes (C/C, C/T and T/T) MTHFR gene showed that the proportion of individuals with a homozygous mutant genotype "T677T" among patients almost 3.5 times higher than that in the control group, the data is statistically reliable (6.6% against 1.9% in control, p<0,04, OR = 3,6).
Significant predominance (p <0.04) of the number of carriers of the homozygous genotype "T677T" in patients with retinal vein
thrombosis may indicate the presence of a pathogenic connection, ie, the association between this kind of genotype with cases of thrombosis.
It was found that mutant allele (677T) MTHFR gene reveals 24% more often in men than in women (15,9%) and the figure for this gene among the control group was 11,2%.
The analysis of the frequency of homozygous genotype polymorphism C677T MTHFR gene in the group of patients demonstrates that among men the frequency of the mutant allele T/T is very high at 10.8%, which is 7,7 times more likely than in women (1,4%) and 5,7 times more than in the control group (1,9%).
Analysis of the distribution of genotypes of DNA polymorphisms, depending on the gender of the patient revealed a number of differences. Statistically significant prevalence of "T677T" MTHFR gene carriers in a group of males (x2 = 6.4; P = 0,02; OR = 8,3; 95% CI 1.021, 66.9) with retinal vein thrombosis was revealed. In the group of women patients, carrier heterozygous genotype "C/T" (28% against 26,5%) determined more than in men. In the control group of men with heterozygous carriage type "C/T" was 1.8 times more than women, but the differences were not significant (X2 = 0,4; P = 0,5; OR = 0,5; 95% CI 0.0427, 5.413).
G/G G/A A/A
BRVO nonischemic type BRVO ischemic type CRVO nonischemic type CRVO ischemic type
2°A
39,50%
11,80%
46,70%
0% 10% 20% 30% 40% 50% Figure 1. Frequency distribution of genotypes of factor FII in subgroups of patients with retinal vein thrombosis
Figure 2. Frequency distribution of genotypes of factor FV in subgroups of patients with retinal vein thrombosis
0% 5% 10% 15%20%25%30% Figure 3. Frequency distribution of MTHFR genotypes in subgroups of patients with retinal vein thrombosis
Studies have revealed the presence of homozygous genotype of MTHFR factor. Homozygous genotype of "T677T MTHFR gene" is more common in the subgroup of patients with ischemic type of CRVO (central vein retinal occlusion) - 4.6%, in the subgroup of patients with nonischemic type of CRVO — 1.3% and ischemic type of branch retinal vein occlusion (BRVO) — 0, 65%.
The homozygous genotype G1691A FV and FII genes ofblood coagulation were not observed in patients of the main group.
Conclusions: 1. The results of studies show that carriers of mutant alleles of FII gene and mutant alleles of the gene FV factor are out of risk of thrombosis.
2. Homozygous genotype of "MTHFR gene T677T" often prevails in the subgroup ofpatients with ischemic type of CRVO — 4.6%.
3. Statistical analysis revealed a predominance of homozy-gous genotype of "T677T MTHFR gene" in the main group of patients. The risk of retinal vein thrombosis in carriers of this genotype is 3,5 times higher than in individuals without this genotype (X2 = 4.1; P = 0.04; OR = 3.5; 95% CI 0.9689, 13.31).
4. The frequency of "T677T MTHFR gene" genotype was 8.3 times more common in males compared with the females (X2 = 6.4; P = 0.02; OR = 8.3; 95% CI 1.021-66.9).
References:
Tankovskiy V. E. Retinal vein thrombosis. - M., 4-H^HAnaA Milit.pub, - 2000. - 262 p.
Katsnelson L. A. Vascular eye diseases./L. A. Katsnelson T. I. Forofonova AYa. Bunin. - M.: Medicine. - 1990. - 270 p. Tultseva S. N. Retinal vein occlusion (etiology, pathogenesis, clinical manifestations, diagnosis, treatment)/S. N. Tultseva, Yu. S. Astak-hov. - Sankt-P.: N-L pub. - 2010. - 112 p.
Astakhov Yu. S. Retinal vein thrombosis: etiology, pathogenesis, clinical manifestations, diagnosis, treatment/Yu. S. Astakhov, N. N. Pe-trishev, S. N. Tultseva//Manual for physicians. - Sankt-P.: S-Pt MU, - 2005. - 60 p.
Lisenko V. S. Thrombocytopathy and its role in hemorrhagic syndrome at vascular eye diseases/V. S. Lisenko, A. I. Mukha, A. Ya .Buninet al.//Journal of ophthalmology. - 2001. - No 1. - P. 24-26.
Astakhov Yu. S. Thrombophilia in pathogenesis of retinal vein thrombosis. Yu. S. Astakhov, N. N. Petrishev, T. S. Varganov, S. N. Tult-seva//Journal of ophthalmology. - 2008. - No 3. - P. 56-58.
BombeliT., Basic A., Fehr J. Prevalence ofhereditary thrombophilia in patients with thrombosis in different venous systems. Am. J. He-matol. - 2002; 70: - P.126-132.
Khan S., Dickerman J. D. Hereditary thrombophilia//Thrombosis J. - 2006. - V. 4. - No 15. - P. 35-40.
Doix S., Mahrousseh M., Jolak M. e. a. Factor V Leiden and myocardial infarction: a case, review of the literature with a meta-analy-sis//Ann CardiolAngeiol (Paris). - 2003. - V. 52, - N 3. - P. 143-149. 10. Kim R.J, Becker R. C. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolatereductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J. - 2003 Dec; - 146 (6): -948-57. Review.
4.
5.
6.
7.
9.
