α-1-Antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated with a lacunar type of ischemic cerebrovascular disease

Abstract

α-1-Antichymotrypsin (ACT) is a plasma protease inhibitor belonging to the serpine superfamily; it has many functions, and thus qualitative change in ACT is likely to result in specific diseases. We previously reported a variant AACT (ACT Isehara-1, Met389Val, A1252G) in patients with ischemic cerebrovascular disease (CVD). The present study was designed to examine the association of the variant with ischemic CVD, in 87 patients and 397 agematched controls. We found that the frequency of the A1252G variant (ACT Isehara-1) was higher in the group with ischemic CVD than in the control group (P ϭ 0.0397), which appeared to be independent of known risk factors. We subdivided the CVD group into lacunar and atherothrombotic subgroups. Further analysis by subtype of ischemic CVD showed an association of ACT Isehara-1 with lacunar infarction (P ϭ 0.0036). These results suggest that ACT Isehara-1 is a new genetic risk factor for ischemic CVD, especially lacunar-type infarction, in Japan.

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

“…Only the intron 4ab genotype of the eNOS gene was associated with isolated lacunar infarction and the AGT-20C allele may be a risk factor for leukoaraiosis [24,25,26,27]. Other studies have reported a strong association of the angiotensin-converting-enzyme genotype to lacunar stroke [28, 29] as well as a –174G/C polymorphism of interleukin 6 [30, 31] and a gene variant of α 1 -antichymotrypsin – a plasma protease inhibitor [32]. …”

Transcriptional analysis of the molecular basis of human kidney aging using cDNA microarray profiling

“…CSPG2 is both a component basement membrane [42] and was shown to be a direct target of p53 [43]. The SERPIN3A, which may be a causative of atherothrombotic infarction [44], was examined for decreased expression in the older age groups. Similarly, biphenyl hydrolase-like (BPHL), primarily expressed in liver and kidney, has a potential enzymatic role in detoxification processes, and was proposed to be reduced with age.…”

SERPINA3 (aka alpha-1-antichymotrypsin)

“…The levels of ACT are elevated in the serum of individuals with malignant disease. ACT has been detected in the nuclei of pancreas, stomach, breast, hepatic and lymphatic cancers despite not being present in the nucleus of normal tissues (48)(49)(50). Within these carcinomas, ACT has been shown to bind to DNA polymerase alpha and DNA primase, suggesting a role in protection against tumorigenesis by inhibiting DNA replication (48,50).…”

“…ACT has been detected in the nuclei of pancreas, stomach, breast, hepatic and lymphatic cancers despite not being present in the nucleus of normal tissues (48)(49)(50). Within these carcinomas, ACT has been shown to bind to DNA polymerase alpha and DNA primase, suggesting a role in protection against tumorigenesis by inhibiting DNA replication (48,50). Elevated serum ACT may be a potential biomarker for cancers of the pancreas (51), gastrointestinal tract (52) and lung (53).…”