| 1 | Mol. Biol. Rep. 2013 Oct 40: 5607-14 |
|---|
| PMID | 24065520 |
| Title | Genetic variants in transforming growth factor-? gene (TGFB1) affect susceptibility to schizophrenia. |
| Abstract | Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology of schizophrenia. The immune theory of schizophrenia is supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background of schizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association between schizophrenia susceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 -330T>G, rs2069756), interleukin-6 (IL-6 -174G>C, rs1800795), interferon-? (IFNG +874T>A, rs2430561) as well as for the first time transforming growth factor-?1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects with schizophrenia and 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients with schizophrenia and healthy controls (p < 0.05). The risk of schizophrenia was more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism and schizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Adv Gerontol 2015 -1 28: 228-47 |
|---|
| PMID | 26856084 |
| Title | GENETICS OF HUMAN AGE RELATED DISORDERS. |
| Abstract | Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. |
| SCZ Keywords | schizophrenia |
| 3 | Schizophr. Res. 2015 Dec 169: 1-9 |
|---|
| PMID | 26481614 |
| Title | Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population. |
| Abstract | schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed. |
| SCZ Keywords | schizophrenia |
| 4 | Neuropsychiatr Dis Treat 2015 -1 11: 575-84 |
|---|
| PMID | 25784812 |
| Title | Sex differences in TGFB-? signaling with respect to age of onset and cognitive functioning in schizophrenia. |
| Abstract | There are studies showing that gene polymorphisms within the transforming growth factor-? (TGF-?) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-? level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale - Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-? levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-? level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-? level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-? signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients. |
| SCZ Keywords | schizophrenia |