engleski

Angiotensin converting enzyme gene I/D polymorphim is not associated with schizophrenia in a Croatian population

Because angiotensin converting enzyme (ACE) plays an important role in dopamine system functioning in the brain and the insertion/deletion (I/D) polymorphism of a 287 nucleotide fragment of the ACE gene correlates with enzyme activity, several studies have investigated the role of ACE I/D polymorphism in psychiatric diseases (Segman et al., 2002 ; Crescenti et al., 2009). Two recent studies yielded contradictory results: the D allele was identified as a protective factor in a Spanish population, while a protective effect toward schizophrenia and bipolar disorder was attributed to the I allele in a Turkish population (Crescenti et al., 2009 ; Kucukali et al., 2010). We tested whether schizophrenia risk was associated with ACE I/D polymorphism in a Croatian population, and examined its possible impact on schizophrenia symptom severity. Our study group consisted of 211 Croatian patients (115 male, 96 female) who met DSM-IV criteria for schizophrenia (n = 187) and schizoaffective disorder (n = 24), and 270 healthy blood donors (135 male, 135 female). All participants gave informed consent for the analysis. The study was approved by the Ethics Committee of the School of Medicine, University of Rijeka, Croatia. Genotyping was performed by polymerase chain reaction (PCR) as previously described (Rigat et al., 1990). To exclude mistyping of the heterozygotes as DD homozygotes, all DD genotype samples were confirmed with insertion-specific PCR (Shanmugan et al., 1993). The significance of differences in genotype and allele frequencies between patients and controls was determined using the χ2 test. Potential correlation between Positive and Negative Symptom Scale (PANSS) scores and I/D polymorphism was tested using linear regression analysis (stepwise selection), adjusted for age at PANSS assessment and sex, in patients with schizophrenia. PANSS evaluation was performed during the last hospitalization due to a psychotic episode. P-values < 0.01 were considered statistically significant. Allelic and genotypic frequencies of I/D polymorphisms were consistent with Hardy-Weinberg equilibrium and were not significantly different between groups. Allele frequencies were 230 (D) and 192 (I) in the patient group, and 285 (D) and 255 (I) in the control group. Genotype frequencies were 0.299 (DD = 63), 0.493 (ID = 104) and 0.208 (II = 44) in the patient group, and 0.274 (DD = 74), 0.507 (ID = 137) and 0.219 (II = 59) in the control group. Therefore, our data did not support results from Spanish or Turkish samples. However, after adjusting for sex and age at PANSS assessment we observed a significant correlation between ACE genotype and psychopathology evaluated by PANSS. Increased negative and total PANSS scores were significantly correlated with the number of D alleles (b = 0.26, F = 7.803 ; P = 0.006 and b = 0.29, F = 7.557 ; P = 0.002, respectively). Increased symptom severity of the general psychopathology scale in males with schizophrenia could also be attributed to the number of D alleles (b = 0.37, F = 9.910 ; P = 0.008). This is the first study reporting significant correlation between clinical expression of illness and I/D polymorphic variants. I/D polymorphism may affect symptom severity by modulating ACE expression/activity. Further studies in other populations/ethnic groups may help clarify the relationship between ACE activity and schizophrenia.

angiotensin converting enzyme gene; I/D polymorphism; schizophrenia

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