1) The document discusses genetic factors that can predispose individuals to thrombosis or hypercoagulable states. It focuses on a study of 158 patients in Uzbekistan. 2) The study found that 50% of subjects carried a mutation in the MTHFR gene, with 43.1% being heterozygous and 6.9% homozygous. Lower rates of around 1.7% carried mutations in the prothrombin and Factor V genes. 3) The conclusion is that the MTHFR mutation, by increasing homocysteine levels, is a major genetic risk factor for hypercoagulability in the population of Uzbekistan, unlike Western populations where prothrom

1. Genetic factors associated with
predisposition for thrombosis
Orzu Yuldasheva
MUA Fall 2015

2. 1854 Rudolph Virchow
Factors precipitating hypercoagulable state/
Thrombophilias
I. Decreased blood flow (venous stasis)
II. Inflammation of or near the blood vessels
(vascular endothelial injury)
III. Intrinsic alterations in the nature of the
blood itself
Background Information

3. Hypercoagulable states
Etiology
• Inherited
• Aquired
• Both
Types
• -venous thrombosis
(most common)
• -arterial thrombosis
• -both

4. Acquired
 Advanced age
 prolonged immobilization
 Surgery
 Fractures
 use of oral contraceptives
 hormone replacement
therapy
 Pregnancy/puerperium
 Cancer
 And many more
VENOUS THROMBOSIS
Risk factors
Inherited
 Mutation in genes encoding for
o protein C
o protein S
o factor V Leiden
o MTHFR (methylene
tetrahydrofolate reductase)
 Hyperhomocysteinemia
 elevated concentrations of
factors II, VIII, IX, XI and
fibrinogen

5. Purpose of study
• To identify mutation in genes coding for
coagulation cascade proteins
• Identify the frequency of those mutations in
population of Uzbekistan.

7. Materials and Methods
Subjects of study -158 patients aged from 17 to 65
Step I - Identify presence of mutations in genes
coding for proteins of coagulation cascade.
Step II- Statistical analysis of the mutations
discovered
Factor V Leiden
FII (Prothrombin)
MTHFR (methylene tetrahydrofolate reductase)

8. Results
Total number of subject in study -158
1.7% were carriers of genes coding for
Prothrombin
1.7 % subjects had mutation in genes coding for
Factor V
50% -carriers of gene coding for mutant MTHFR
From those
43.1% were heterozygotes
6.9% were homozygotes

9. Statistical analysis
1.70%
1.70%
46.60%
6.90%
43.10%
50.00%
Prothrombin
Factor V
Unidentified
Homozygous MTHFR
Heterozygous MTHFR
*Unidentified- no know mutations associated with Hypercoagulability were identified

10. Distribution of most frequent mutations leading to thrombophilias in USA.
*Data obtained from Cleveland Medical Clinic

11. MTHFR mutation
• It was identified that this mutation follows
autosomal-recessive pattern of inheritance,
therefore clinical symptoms were only
observed in homozygotes.
• Altered enzyme, determined by mutant MTHFR
is thermolabile, and characterized by
decreased enzymatic activity which leads to
deffierent degrees of hyperhomocysteinemia
resulting in hypercoagulability and vascular
events.

12. Cytogenetic Location: 1p36.3
Molecular Location on chromosome 1:
base pairs 11,785,729 to 11,806,102
Single point mutation in the coding region for the MTHFR binding site
(exon 4) is autosomal recessive, leads to the substitution of a valine for an
alanine, and results in a thermolabile variant of the MTHFR (tlMTHFR)

13. Conclusion
• As the results of study show the most
common mutation is MTHFR, which leads to
increased level of homocysteine,
development of blood clots and
cardiovascular abnormalities. Whereas,
Factor V Leiden and Prothrombin mutations
are more common in Western regions,
especially in Europe and USA.