Human heat shock protein gene polymorphisms and sudden infant death syndrome.

Abstract

Comparison of the frequency of occurrence of restriction fragment length polymorphisms in control human DNAs and DNAs from infants dying from sudden infant death syndrome has indicated no significant difference in the case of restriction fragment length polymorphisms associated with the heat shock protein genes hsp7O and hsp9O. A highly significant difference was detected, however, in the case of the specific restriction fragment length polymorphisms detected by an hsp6O gene probe in MspI digests. (Arch Dis Child 1996;75:451-452) Keywords: heat shock proteins, restriction fragment length polymorphisms, sudden infant death syndrome, heat shock protein 60.Heat shock proteins play a central part in the normal physiology of cells.' Although they appear to be involved in the acquisition and maintenance of thermotolerance, other major roles include the repair of denatured cell proteins and functions as molecular 'chaperones' in the intracellular transmembrane transport of cellular proteins and in the construction of complex quaternary cellular protein structures. At present the cause of sudden infant death syndrome (SIDS) is unclear. Some deaths have been attributed to fever-like disorders,2 possibly brought on by overwrapping or by a virus infection. A possibility is that infants are susceptible to SIDS because some of the heat shock proteins are not produced or are defective, thus providing inadequate thermal protection. This could arise from defects in the DNA associated with genes encoding critical heat shock proteins. Results and discussion An initial screen of healthy human subjects was undertaken to determine whether sequence probes to the heat shock protein genes, hsp6O, hsp7O, and hsp9O could reveal any restriction fragment length polymorphisms (RFLPs). A panel of 26 genomic DNA samples was digested with 19 different restriction enzymes to detect RFLPs. Use of the hsp7o probe detected variations in these control samples digested with BgII, PstI and PvuII, as previously reported by Goate et al. 4 The DNAs digested with MspI or ScaI were also polymorphic for hsp6O, and the hsp90 probe detected variations in samples digested with Sau961. The frequency of the variable fragments was determined for all polymorphisms (table 1). The RFLPs detected using the hsp60 probe were more complex than those found using the hsp7O probe. With MspI, 16 constant fragments and six variant fragments were detected in 26 individuals. There was one hsp9o associated polymorphism, detected with Sau961 digested DNA. Nine of the fragments were invariant, whereas two others displayed a polymorphism characteristic of a two allele system.To determine if there was any difference in the nature of heat shock protein gene polymorphisms in infants dying from SIDS compared with the controls, 12 DNA samples from SIDS infants were examined with the same 19 restriction enzymes used in the initial screening for heat shock protein polymorphisms. Although the sample size of SIDS DNAs used was small it was sufficiently large to detect frequent...

Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential

“…These results suggest that HSPD1 and HSPE1 gene variations represent no significant factor for the development of SIDS. The MspI RFLP observed with a HSPD1 cDNA probe, and reported to be overrepresented in a SIDS cohort (Rahim et al 1996), most likely represents a polymorphism that resides in a HSPD1 pseudogene, since the MspI sites in this chromosome region predicted by the complete human genome sequence are not compatible with the chromosomal DNA fragments observed by these authors (data not shown). Furthermore, the statistical significance of the finding has been challenged (Tanner et al 1997).…”

“…Genetic predisposition group Sixty-one cases of sudden infant death syndrome (SIDS); RFLP analysis has indicated overrepresentation of a certain HSPD1 genotype in a group of SIDS cases (Rahim et al 1996), and heat stress has been reported as risk factor for SIDS (Byard and Krous 2003).…”

Functional single-nucleotide variant of HSPD1 in sudden infant death syndrome

“…However, to date only two studies investigated HSPD1 genetic alterations in SIDS and these brought forth contradictory results as to their potential impact: Rahim et al analyzed an MspI restriction fragment length polymorphism in HSPD1 and reported one specific fragment to be significantly underrepresented in the SIDS group (22). The meaning of this study's findings is limited, however, by its small collective (n = 12) and its lack of correction for multiple testing in statistical analysis (23).…”

Genetic variation in heat shock protein 60 gene and coronary heart disease in China: tagging-SNP haplotype analysis in a case-control study

“…To the best of our knowledge, however, only two previous studies have examined the associations between the variability in hsp60 gene and human diseases. One French study indicated that the G+292A (dbSNP: rs41350646) polymorphism in hsp60 was associated with hereditary spastic paraplegia (Hansen et al 2002), and another suggested that one MspI polymorphism was related to sudden infant death syndrome (Rahim et al 1996). No study has investigated the association between hsp60 gene polymorphisms and CHD.…”