Abstract
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcohol-metabolizing enzymes. While alcohol use is associated with spontaneously deep intracerebral haemorrhage (SDICH), particularly in males, the activities and genetic variants of ADH and ALDH may affect SDICH development. This case-control study was conducted to identify the interaction of alcohol use and SDICH with five single-nucleotide polymorphisms (SNPs): ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs671, ALDH2 rs886205, and ALDH2 rs4648328. We enrolled 208 patients with SDICH and 244 healthy controls in a Taiwanese population. ALDH2 rs671 was significantly associated with SDICH in the dominant (P < 0.001) and additive models (P = 0.007). ALDH2 rs4648328 was borderline significantly associated with SDICH in the recessive (P = 0.024) or additive models (P = 0.030). In alcohol-using patients, the ALDH2 rs671 GG genotype was associated with SDICH risk compared to the GA+AA genotype (P = 0.010). ADH1B rs1229984, ADH1C rs2241894, and ALDH2 rs886205 did not demonstrate association with SDICH. Thus, the ALDH2 rs671 GG genotype is a risk factor for SDICH. Because the genetic distributions of ALDH2 rs671 exhibited strong ethnic heterogeneity, further studies in different populations are needed to validate these findings.
Highlights
Primary intracerebral haemorrhage (ICH), accounting for 22–35% of all cases of stroke in Asian populations[1], is the most devastating stroke subtype with high rates of death and long-term disability in adults[2,3]
We conducted a case-control study to investigate the associations of genetic variants in Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), including ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs[671], ALDH2 rs886205, and ALDH2 rs4648328, and spontaneously deep intracerebral haemorrhage (SDICH) in a Taiwanese population
ALDH2 rs4648328 could be associated with SDICH in the recessive model (OR = 2.4, 95% CI: 1.1–5.1, P = 0.024) and additive model (OR = 1.4, 95% CI: 1.0–1.9, P = 0.030) with boardline significance
Summary
Primary intracerebral haemorrhage (ICH), accounting for 22–35% of all cases of stroke in Asian populations[1], is the most devastating stroke subtype with high rates of death and long-term disability in adults[2,3]. Sixty to eighty percent of primary ICH cases occur at the non-lobar region, including the basal ganglia, thalamus, brain stem, and cerebellum, and are known as spontaneously deep intracerebral haemorrhage (SDICH)[4]. Numerous factors, such as hypertension and alcohol use, have been proposed to contribute to SDICH development[5,6]. Individuals with the ALDH2 rs[671] A allele have higher prevalence of hypertension, cardiovascular risk factors, and cerebral infarction[15]. Presence of the ALDH2 rs[671] A allele could be a risk factor for cerebral infarction in Han-Chinese population[15]. We conducted a case-control study to investigate the associations of genetic variants in ADH and ALDH, including ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs[671], ALDH2 rs886205, and ALDH2 rs4648328, and SDICH in a Taiwanese population
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