Sacide PEHLİVAN, Pınar AYDIN ÇETİNAY, Hasan Mervan AYTAÇ, Atilla Mehmet UYSAL, Ülgen SEVER, Mustafa PEHLİVAN

Investigation of Catechol-O-Methyltransferase and Cannabinoid Receptor 2 gene variants in tobacco use disorder or tobacco use disorder and schizophrenia comorbidity

Objective: The purpose of this study was to investigate whether functional variants of Catechol-O-Methyltransferase (COMT) (rs4680) and Cannabinoid Receptor 2 (CNR2) (rs2501432) genes play a role in tobacco use disorder (TUD) or tobacco use disorder and schizophrenia (TUDSch) comorbidity. Methods: This study consisted of 163 participants with TUD, 60 participants with TUDSch, and 106 gender-, age- and ethnicity-matched non-smoker controls (HNC). While the TUD and TUDSch were diagnosed according to the DSM-5, the severity of TUD was rated according to the Fagerstrom Test for Nicotine Dependence. Genotyping of COMT and CNR2 genes was determined using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Results: Distributions of genotypes and allele frequencies were compared among the groups. Patients with TUDSch had higher frequency of COMT Val/Val genotype compared to the TUD and HNC groups (p=0.001, p=0.034, respecttively). Patients with TUD had higher frequency of Val/Met genotype than TUDSch and HNC groups (p=0.001, p=0.033, respectively). The frequency of the Val allele was higher in TUDSch than the HNC group, whereas the frequency of the Met allele was higher in TUD than in the TUDSch group (p=0.047, p=0.001, respectively). Additionally, patients with TUD had higher frequency of TT CNR2 genotype than the HNC group (p=0.019). Conclusion: While the Val/Val genotype of the COMT gene is associated with an increased risk for TUDSch, the Val/Met genotype is associated with an increased risk for TUD. Additionally, the TT CNR2 genotype was associated with increased risk for TUD in the Turkish population.

Tütün kullanım bozukluğu veya tütün kullanım bozukluğu ve şizofreni komorbiditesinde Katekol-O-Metiltransferaz ve Kannabinoid Reseptör 2 gen varyantlarının incelenmesi

Amaç: Bu çalışmanın amacı, Katekol-O-Metiltransferaz (COMT) (rs4680) ve Kannabinoid Reseptör 2 (CNR2) (rs2501432) genlerinin işlevsel varyantlarının tütün kullanım bozukluğu (TUD) veya tütün kullanım bozukluğu ve şizofreni (TUDSch) komorbiditesinde rol oynayıp oynamadığını araştırmaktır. Yöntem: Bu çalışmanın örneklemini 163 TUD, 60 TUDSch ve 106 cinsiyet, yaş ve etnisite eşleşmeli sigara içmeyen kontrol grubu (HNC) oluşturmuştur. TUD ve TUDSch tanıları DSM-5 tanı ölçütlerine göre konulurken, TUD şiddeti Fagerstrom Nikotin Bağımlılığı Testine göre derecelendirilmiştir. COMT ve CNR2 genlerinin genotiplendirilmesi, polimeraz zincir reaksiyonu ve restriksiyon parça uzunluk polimorfizmi yöntemi kullanılarak belirlenmiştir. Bulgular: Gruplar arasında genotip ve allel frekans dağılımları karşılaştırılmış olup COMT val/val genotipi sıklığı TUDSch hastalarında, TUD ve HNC gruplarına göre daha fazla bulunmuştur (sırayla p=0.001, p=0.034). Val/met genotipi sıklığı, TUD hastalarında, TUDSch ve HNC gruplarına göre daha fazla bulunmuştur (sırayla p=0.001, p=0.033). Val alelinin sıklığı TUDSch hasta grubunda HNC grubuna göre daha fazla saptanmış, met alelinin sıklığı ise TUD hasta grubunda, TUDSch hasta grubuna göre daha fazla bulunmuştur (sırayla p=0.047, p=0.001). Ek olarak, TUD hastalarında TT CNR2 genotipi sıklığı HNC grubuna göre daha fazla saptanmıştır (p=0.019). Sonuç: COMT geninin val/val genotipi TUDSch için artmış bir riskle ilişkilendirilmiş olup, val/met genotipi ise TUD için artmış riskle ilişkilendirilmiştir. Ek olarak, Türk popülasyonunda TT CNR2 genotipi artmış TUD riski ile ilişkili bulunmuştur.

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