Association and Haplotype Analysis of the PON1, ITGB3 and CYP3A4 Genes, Strong Candidates for Familial Coronary Artery Disease Susceptibility

Abstract

Objective: Genetic predisposition is very common among the patients with coronary artery disease (CAD), a complex and multifactorial disease. Our objective was to determine the possible association between the most remarkable functional variants in the paraoxonase 1(PON1), cytochrome P450 3A4 (CYP3A4), integrin subunit beta 3 (ITGB3) genes and familial CAD. Materials and Methods: We included 117 patients diagnosed with familial CAD and 99 healthy subjects with no family history of CAD. PON1 Q192R, PON1 L55M, CYP3A4*1G and ITGB3 L33P single nucleotide polymorphisms were genotyped using the Sequenom MassARRAY system. Results: Comparison of genotype and allele frequencies in inheritance models of polymorphisms between the patient and control groups did not reveal any significant findings related to CAD. Stratified analysis by gender did also not display any association both in females and males. There was no significant difference in the frequencies of the haplotypes of the PON1 Q192R and L55M polymorphisms between the groups. Conclusions: Our findings confirmed previous studies that did not consider PON1, CYP3A4 and ITGB3 genes as risk loci. The fact that our study was conducted only in patients with familial CAD shows the originality and importance of our results.

Keywords

• CYP3A4
• familial coronary artery disease
• PON1
• ITGB3

Ailesel Koroner Arter Hastalığına Yatkınlıkta Güçlü Adaylar PON1, ITGB3 ve CYP3A4 Genlerinin Hastalıkla İlişkisi ve Haplotip Analizi

Öz

Amaç: Kompleks ve multifaktöriyel bir hastalık olan koroner arter hastalığında (KAH) genetik yatkınlık çok yaygındır. Amacımız; paraoksonaz 1(PON1), sitokrom P450 3A4 (CYP3A4), integrin subunit beta 3 (ITGB3) genlerindeki en dikkat çekici fonksiyonel varyantlar ile ailesel KAH arasındaki olası ilişkiyi belirlemekti. Materyal ve Metot: Çalışmamıza ailesel KAH tanısı almış 117 hasta ile ailesinde KAH öyküsü olmayan 99 sağlıklı bireyi dahil ettik. PON1 Q192R, PON1 L55M, CYP3A4*1G ve ITGB3 L33P tek nükleotid polimorfizmleri Sequenom MassARRAY sistemi kullanılarak genotiplendirildi. Bulgular: Polimorfizmlerin kalıtım modellerindeki genotip ve allel frekanslarının hasta ve kontrol grupları arasında karşılaştırılması KAH ile ilişkili anlamlı bir bulgu ortaya çıkarmadı. Cinsiyete göre tabakalı analiz yöntemi de hem kadınlarda hem de erkeklerde herhangi bir ilişki göstermedi. PON1 Q192R ve L55M polimorfizmlerinin haplotip frekansları hasta ve kontrol grupları arasında analiz edildiğinde ise yine anlamlı bir fark yoktu. Sonuç: Bulgularımız, PON1, CYP3A4 ve ITGB3 genlerini risk lokusları olarak kabul etmeyen önceki çalışmaları doğrulamış oldu. Çalışmamızın sadece ailesel KAH hastalarında yapılmış olması, sonuçlarımızın özgünlüğünü ve önemini göstermektedir.

Anahtar Kelimeler

• Ailesel koroner arter hastalığı
• CYP3A4
• PON1
• ITGB3

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