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


CONCLUSIONS
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.
Kim
Jung Jin
JJ
Department of Psychiatry, The Catholic University of Korea College of Medicine, Kangnam St Mary's Hospital, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
Mandelli
Laura
L
Lim
Suzy
S
Lim
Hyun Kook
HK
Kwon
Oh Joo
OJ
Pae
Chi Un
CU
Serretti
Alessandro
A
Nimgaonkar
Vishwajit L
VL
Paik
In-Ho
IH
Jun
Tae-Youn
TY
D000328:Adult; D001244:Association; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins