RGD Reference Report - Association analysis of heat shock protein 70 gene polymorphisms in schizophrenia. - Rat Genome Database

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Association analysis of heat shock protein 70 gene polymorphisms in schizophrenia.

Authors: Kim, JJ  Mandelli, L  Lim, S  Lim, HK  Kwon, OJ  Pae, CU  Serretti, A  Nimgaonkar, VL  Paik, IH  Jun, TY 
Citation: Kim JJ, etal., Eur Arch Psychiatry Clin Neurosci. 2008 Jun;258(4):239-44.
RGD ID: 5147596
Pubmed: PMID:18299791   (View Abstract at PubMed)
DOI: DOI:10.1007/s00406-007-0791-6   (Journal Full-text)

OBJECTIVES: Heat shock proteins (HSPs) are a promising candidate gene in schizophrenia as they are believed to play a protective role in the central nervous system. An alteration in the titers of antibodies to the HSPs in schizophrenia patients has been suggested. Association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B) and schizophrenia has been reported. Therefore, this study investigated the association between an enlarged set of SNPs at HSP70 gene and schizophrenia. METHODS: Two hundred and ninety-four patients with schizophrenia and 287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70 were performed using pyrosequencing method. Haploview 3.2 was used to generate a linkage disequilibrium map and to test for Hardy-Weinberg equilibrium. Single locus and haplotype-based associations were tested. Tests for associations using and multi-marker haplotypes were performed by using a COCAPHASE v2.403. Association of SNP markers and clinical variables were analyzed by analysis of variance. RESULTS: Significant association was detected at rs2075799 (allele A, X2 = 8.03, df = 1, P = 0.0046), but not at rs2227956 (P = 0.28), rs1043618 (P = 0.88), rs562047 (P = 0.47) or rs539689 (P = 0.32). In fact, the rs2075799*G/A genotype was more represented in patients with schizophrenia than in controls (X2 = 8.23, df= 1, P = 0.0041). Haplotype based associations were also detected (global P value 0.000003); the T-A-C-C-G haplotype was more prevalent among the patients (odds ratio, OR 5.95). Sliding windows analysis revealed a major contribution from rs2227956 and rs2075799 (global-P value 0.0075), with T-A haplotype significantly associated with schizophrenia. There was no evidence of an association between the clinical variables and schizophrenia across the genotypes. CONCLUSION: Our results raise the possibility that HSP70 gene (i.e., haplotypes of rs2075799) might be implicated in the development of schizophrenia, although limited by rare haplotypic association with the disease. Hence further studies from different ethnics should be performed to confirm these results.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
schizophrenia  IAGP 5147596DNA:missense mutation more ...RGD 
schizophrenia  IAGP 5147596DNA:silent mutation and haplotype:cds: (rs539689) (human)RGD 
schizophrenia  IAGP 5147596DNA:silent mutation more ...RGD 
schizophrenia  ISOHSPA1A (Homo sapiens)5147596; 5147596DNA:missense mutation more ...RGD 
schizophrenia  ISOHSPA1B (Homo sapiens)5147596; 5147596DNA:silent mutation and haplotype:cds: (rs539689) (human)RGD 
schizophrenia  ISOHSPA1L (Homo sapiens)5147596; 5147596DNA:silent mutation more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Schizophrenia  IAGP 5147596DNA:missense mutation more ...RGD 
Schizophrenia  IAGP 5147596DNA:silent mutation and haplotype:cds: (rs539689)RGD 
Schizophrenia  IAGP 5147596DNA:silent mutation more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hspa1a  (heat shock protein family A (Hsp70) member 1A)
Hspa1b  (heat shock protein family A (Hsp70) member 1B)
Hspa1l  (heat shock protein family A (Hsp70) member 1 like)

Genes (Mus musculus)
Hspa1a  (heat shock protein 1A)
Hspa1b  (heat shock protein 1B)
Hspa1l  (heat shock protein 1-like)

Genes (Homo sapiens)
HSPA1A  (heat shock protein family A (Hsp70) member 1A)
HSPA1B  (heat shock protein family A (Hsp70) member 1B)
HSPA1L  (heat shock protein family A (Hsp70) member 1 like)


Additional Information