Girdin is a protein involved in neuronal migration and hippocampal development. It is encoded by the coiled-coil domain-containing 88A (CCDC88A) gene, located on the short arm of chromosome 2 (2p). The CCDC88A gene is modulated by the intergenic single-nucleotide polymorphism (SNP) of the rs1437396, situated 9.5 kb downstream from its transcription stop site. As recent genome-wide research has associated the T allele of the SNP with increased risk of alcohol use disorder (AUD), we wanted to validate this finding in an independent cohort and to test further for an association with comorbid major depressive disorder (MDD). The study included 226 AUD patients (AUD group), 53 patients with comorbid MDD, and 391 controls selected randomly. The participants were genotyped for the rs1437396 polymorphism using the real-time polymerase chain reaction. The association between the rs1437396 polymorphism and increased risk of AUD and AUD+MDD was tested with logistic regression. Our results show significantly higher frequency of the T risk allele in the AUD group (p=0.027) and even higher in the AUD+MDD group (p=0.016). In conclusion, this is the first study that has validated the association between the rs1437396 polymorphism of the CCDC88A gene and AUD with or without MDD. Studies on larger samples of patients are needed to further investigate the mechanism of this association.
Girdin je protein koji sudjeluje u neuronskoj migraciji i razvoju hipokampusa, a kodira ga gen 88A koji sadržava domenu sa smotanom zavojnicom (eng. coiled-coil domain-containing 88A gene, krat. CCDC88A) koja se nalazi na kraćem kraku kromosoma 2 (2p). Gen CCDC88A mijenja se s međugenskim jednonukleotidnim polimorfizmom (eng. single-nucleotide polymorphism, krat. SNP) na mjestu rs1437396, 9,5 kb nizvodno od svojega transkripcijskog završetka. Budući da je u nedavnom istraživanju na razini genoma zamijećena povezanost alela T ovoga polimorfizma s povećanim rizikom od poremećaja zloporabe alkohola (eng. alcohol use disorder), htjeli smo provjeriti tu povezanost u neovisnoj kohorti randomiziranih ispitanika i dodatno ispitati je li polimorfizam povezan i s popratnim povratnim depresivnim poremećajem (eng. major depressive disorder). Ispitivanje je obuhvatilo 226 bolesnika s poremećajem zloporabe alkohola, 51 bolesnika s popratnim povratnim depresivnim poremećajem i 391 kontrolnog ispitanika. Ispitanici su genotipizirani radi utvrđivanja onih koji imaju polimorfizam rs1437396 pomoću polimerazne lančane reakcije u stvarnom vremenu (eng. real-time polymerase chain reaction) te je logaritamskom regresijskom analizom utvrđena povezanost polimorfizma rs1437396 s rizikom od poremećaja zloporabe alkohola s popratnim povratnim depresivnim poremećajem ili bez njega. Naši podatci upućuju na značajno veću učestalost alela T u bolesnika s poremećajem zloporabe alkohola (p=0,027) te na još značajniju učestalost u bolesnika s obama poremećajima (p=0,016). Ovo je prvo istraživanje koje je potvrdilo povezanost između polimorfizma rs1437396 gena CCDC88A i poremećaja zloporabe alkohola s popratnim povratnim depresivnim poremećajem ili bez njega. Daljnja istraživanja mehanizama ove povezanosti potrebno je provesti na većim uzorcima.
Keywords: alel T polimorfizma rs1437396; girdin; major depressive disorder; povratni depresivni poremećaj; rs1437396 T allele.
© 2023 Maria Bonea et al., published by Sciendo.