The haplotype of the CACNA1B gene associated with cerebral infarction in a Japanese population

摘要

Today, cerebral infarction (CI) is one of the main causes of death in the world, although the genetic basis of CI has yet to be determined. CI is now thought to be a multifactorial disease that is affected by several environmental factors and genetic variants (Hassan and Markus 2000).The N-type voltage-gated calcium channels (VGCCs) are expressed primarily in neurons that have various functional roles, although they are especially involved with neurotransmitter release at the sympathetic nerve terminals (Hirning et al. 1988; Toth et al. 1993; Hong and Chang 1995; Vega et al. 1995; Serone and Angus 1999; Catterall et al. 2005). It has been demonstrated that N-type VGCCs regulate the systemic cardiovascular tone. Animal model studies have suggested that blocking the N-type VGCCs can decrease the neuronal damages associated with ischemic brain injury (Valentino et al. 1993; Pringle et al. 1996; Perez-pinzon et al. 1997; Takahara et al. 2004). Voltage-gated calcium channels, which include the N-type, are complex proteins composed of four or five distinct subunits that are encoded by multiple genes (Catterall 2000). Differences within the α1 subunit are related to the differences associated with the actual function, such as conduction pores, voltage sensors and gating apparatus. The α1B subunit is characterized as the N-type voltage-gated calcium channel. Therefore, the human gene encoded α1B subunit (CACNA1B) could be a CI candidate gene. However, at the present time there have been no genetic association studies that have examined the relationship between CI and CACNA1B.The human CACNA1B gene is a single copy gene that spans about 244 kilobase pairs (kb), and is composed of 47 exons that are interrupted by 46 introns (Fig. 1). The gene is located on 9q34. The aim of the present study was to assess the association between the human CACNA1B gene and the occurrence of CI in the Japanese population via a haplotype-based case-control study that used single nucleotide polymorphisms (SNPs).Figure1. Open FigureDownload Powerpoint slideOrganization of the human CACNA1B gene and location of the SNPs. Boxes indicate exons and lines indicate introns. The three arrows show the location of the three SNPs.