Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia‐Pacific region

Background: Apolipoprotein E (APOE) is polymorphic, and may be involved in the pathogenesis and clinical expression of schizophrenia. This study aimed to investigate the frequency of specific APOE genotypes and alleles in a schizophrenic Arab population and evaluate the association of specific APOE types with clinical phenotypes of the disease. Subjects and Methods: Two age-matched groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset of disease, family history of psychosis, disease severity and outcome over the years of illness. APOE genotyping was performed by a validated PCR-RFLP technique. Results and Discussion: Genotype E3E2 and allele E2 were less frequent in the patients with schizophrenia (p = 0.04), and both APOE types tended to be more common in male than female schizophrenic patients (p = 0.08). Schizophrenic patients with a positive family history of psychosis had lower frequencies of genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were least common in patients with an age at onset of disease >31 years (OR: 5.5, 95% CI: 1.1–27.4), particularly in males. Conclusion: APOE genetic polymorphism potentially influences susceptibility to schizophrenia and may be associated with aspects of its phenotypic expression, particularly gender, age of onset and family history of psychotic illness. This relationship of APOE with schizophrenia is likely to be race- and gender-specific.

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“…Each subject was, in addition, assessed in detail clinically and with routine biochemical and hematological tests, as described. [16] .…”

Section: Subjectsmentioning

confidence: 99%

Apolipoprotein E Polymorphism and Clinical Disease Phenotypes in Arab Patients with Schizophrenia

Akanji¹,

Ohaeri²,

Al-Shammri³

et al. 2009

Neuropsychobiology

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“…This is supported by the reported difference in the allele frequencies of this polymorphism, ranging from 0.11 for the minor allele in Northern Italians to 0.19 in the mixed Caucasian sample from Germany, Hungary, and Israel. Association to TNFA may be stronger in Caucasian populations, with Japanese, 65 Chinese, 66,67 Korean 68 and some Asian-Pacific populations 69 failing to show association between TNFA promoter markers and schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor promoter haplotype associated with schizophrenia reveals a linked locus on 1q44

et al. 2004

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Using restriction fragment length polymorphism and pyrosequencing methods, we genotyped two TNFA gene promoter SNPs (ÀG308A, ÀG238A) and analyzed the haplotype structure in 24 Canadian families of primarily Celtic origin. Our results demonstrate that after correction for multiple testing based on simulations of 10 000 replicates of unlinked/unassociated data, there is evidence for association (P ¼ 0.026) of a specific haplotype (À308A, À238G) with schizophrenia and schizophrenia spectrum disorders with a family-based trimmed haplotype linkage disequilibrium test (Trimhap). Stratifying the 22 families with genome scan data by TNFA promoter haplotypes followed by reanalysis of linkage to schizophrenia throughout the genome, we identified few loci that exhibit a considerable increase in LOD/HLOD scores. A locus on chromosome 1q44 (D1S1609) demonstrated a significant increase (P ¼ 0.025) in LOD score from 0.15 to 3.01 with a broad definition of the schizophrenia phenotype and a dominant mode of inheritance. This result replicates a previously reported positive result of linkage of schizophrenia spectrum disorders to this area of the genome. We also illustrated that simulation studies are pivotal in evaluating the significance of results obtained with newer statistical methods, when multiple, but not independent, tests are performed, and when sample stratification is utilized to reduce the impact of heterogeneity or assess the interaction between loci.

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“…The study of 3 promoter variants of the TNF gene (including -G308A polymorphism) in subjects from 4 populations performed by Handoko et al [44] revealed no evidence for the involvement of variants studied to SCH susceptibility. Participating individuals differed strongly in their ethnicity, which resulted in diverse allele frequencies between groups.…”

Section: Discussionmentioning

confidence: 99%

“…A Finnish study pointed out that -308G/G homozygosity was modestly associated with SCH only in male subjects [37] . Finally, 10 other reports from different populations worldwide were negative [42][43][44][45][46][47][49][50][51][52] . However, one of them observed an interaction effect of TNF -238G/A and -308A/A genotypes and a positive family history [43] .…”

Section: Discussionmentioning

confidence: 99%

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Association of Tumor Necrosis Factor –308G/A Promoter Polymorphism with Schizophrenia and Bipolar Affective Disorder in a Polish Population

et al. 2008

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Background/Aims: Schizophrenia (SCH) and bipolar affective disorder (BPAD) are complex disorders with significant participation of genetic risk factors. Several lines of evidence point to the role of shared neurobiological mechanisms and common genetic background in SCH and BPAD. Immune disturbances have been suggested as contributing factor in the pathogenesis of both SCH and BPAD. The gene coding cytokine tumor necrosis factor (TNF) has been the object of a number of association studies in SCH, with ambiguous results. Only 3 such studies were performed in BPAD. The aim of our study was to perform a case-control association analysis of the TNF –308G/A polymorphism in a Polish sample of patients with SCH, BPAD and healthy controls. Methods: We genotyped the TNF –308G/A polymorphism (rs1800629) by PCR-RFLP in 348 patients with SCH, 361 patients with BPAD and in 351 controls. Results: We observed an association of the –308G allele with both SCH (p = 0.008) and BPAD (p = 0.039), and also with a positive family history in patients with SCH (p = 0.048) and BPAD (p = 0.027). For TNF genotypes, the association was only seen in SCH (p = 0.018). Conclusions: Our results may point to an association of the TNF –308G allele and –308G/G genotype with both SCH and BPAD, and to a relationship of the –308G allele with the risk of SCH and BPAD in patients with a positive family history. TNF could be potentially a susceptibility gene, shared between SCH and BPAD. Complex TNF gene studies – based on multiple single-nucleotide polymorphisms and involving haplotype analysis – are necessary for the clarification of currently contradictory findings.

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Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia‐Pacific region

Cited by 31 publications

References 38 publications

Apolipoprotein E Polymorphism and Clinical Disease Phenotypes in Arab Patients with Schizophrenia

Apolipoprotein E Polymorphism and Clinical Disease Phenotypes in Arab Patients with Schizophrenia

Tumor necrosis factor promoter haplotype associated with schizophrenia reveals a linked locus on 1q44

Association of Tumor Necrosis Factor –308G/A Promoter Polymorphism with Schizophrenia and Bipolar Affective Disorder in a Polish Population

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