Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers.

Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and the type of congenitally missing teeth.

ooth agenesis, affecting up to 20% of human population, is one of the most common congenital disorder. The most frequent form of tooth agenesis is known as hypodontia, which is characterized by the absence of one to five permanent teeth excluding third molars. It was considered that hypodontia is especially related with gene mutations which play role in tooth formation. Additionally mutations in PAX9 and/or MSX1 have been identified as the defects responsible for missing permanent molars and second premolars. In some studies it was also found that PAX9 and MSX1 gene mutations may change tooth size. Therefore  in this study all of these factors were investigated. Thirty one patients and 30 controls were enrolled to the study. Information about tooth sizes and type of congenitally missing teeth were collected. MSX1 and PAX9 gene mutations were investigated by direct sequencing. Results were evaluated statistically. As a result, 22 variations were detected in PAX9 in which 18 of them are novel. In addition, 7 variations were found in MSX1 in which 5 of them are novel and one of them lead to amino acid change. Statistically significant relations were found between detected variations and tooth sizes. Any relation between mutations and type of congenitally missing teeth were not detected. In conclusion, especially new mutations which may cause hypodontia, effect tooth size and type of congenitally missing teeth, should be investigated with other researchers for clarifying the mechanism.