An association between minor physical anomalies in schizophrenia and polymorphisms in phospholipase A2 genes

Abstract

Cilj: Neurorazvojna hipoteza shizofrenije implicira abnormalnu regulaciju metaboličke kaskade arahidonske kiseline (AA), a minor anomalije (MA) navode se kao potencijalni markeri abnormalnog razvoja mozga. U radu je istražena moguća povezanost varijacija u trima genima iz superobitelji fosfolipaza (PLA2) čiji su produkti uključeni u signalni put AA s pojavom MA glave i lica u shizofrenih bolesnika. Metode: U istraživanje su uključena 63 ispitanika (32 žene i 31 muškarac) Klinike za psihijatriju KBC-a Rijeka s potvrđenom dijagnozom shizofrenije prema DMS-IV kriterijima. Procijenjeno je 30 varijabli koje opisuju varijacije lica, očiju, nosa, usnica, nepca, jezika i ušiju, te određen ukupan broj MA u svakog ispitanika. Polimorfi zme gena PLA2G4A (rs10798059, G/A ili BanI polimorfi zam), PLA2G6A (rs4375, C/T) i PLA2G4C (rs1549637, A/T) analizirali smo PCRRFLP metodom. Rezultati : Pronađena je stati sti čki značajna povezanost između zbroja MA i PLA2G4C genoti pa (tauPLA2G4C = 0,214; P = 0,014) pri čemu je medijan zbroja MA bio najviši u TT homozigota i iznosio 13 (raspon od 10 do 16). Također smo utvrdili stati sti čki rubno značajnu interakciju PLA2G4A i PLA2G6A genoti pova, pri čemu je najviši medijan zbroja MA nađen u homozigota GG/CC (14; raspon od 10 do 22), odnosno u odsutnosti PLA2G4A-A ili PLA2G6A-T alela (P = 0,058). Zaključak: Rezultati upućuju na moguću povezanost varijacija u genima uključenim u rani razvoj živčanog sustava s pojavom MA glave i lica u shizofrenih bolesnika.Aim: The neurodevelopmental hypothesis of schizophrenia implicates abnormal regulati on of the arachidonic acid (AA) metabolic cascade while minor physical anomalies (MPAs) are indicated as a potenti al markers of abnormal brain development in pati ents with schizophrenia. We tested whether risk for MPAs was associated with variati ons in three genes of phospholipase A2 (PLA2) superfamily as PLA2s play an important role in signaling pathway of AA. Methods: 63 pati ents (32 females and 31 males) from the Psychiatry Clinic, Clinical Medical Centre Rijeka, were recruited for this study; the diagnosis of schizophrenia was confi rmed using DSM-IV criteria. We investi gated 30 MPAs of the head and face regions, and correlated their total number with genotype and allelic variants of polymorphisms in genes PLA2G4A (rs10798059, G/A or BanI polymorphism), PLA2G6A (rs4375, C/T variation) and PLA2G4C (rs1549637, A/T variation). Genotyping was performed by PCR-RFLP method. Results: Significant correlati on was found between MPA total score and PLA2G4C genotype (tauPLA2G4C=0,214; P=0,014); the highest median was found in TT homozygotes (13; range=10-16). A trend for synergisti c eff ect of two polymorphisms, each one in PLA2G4A and PLA2G6A genotypes, was also detected. The highest MPA score median was found in GG/CC homozygotes (14; range=10-22; P=0,058) or in the absence of PLA2G4A-A and PLA-2G6A-T alleles. Conclusions: The results suggested possible associati on between parti cular variati ons in the genes crucial during early development of central nervous system (genes of the PLA2 superfamily) with higher total number of MPAs of the head and face