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K Gormley

Publications and source records attributed to K Gormley.

4 recordsLinked to original sources
PubMed2006

Polymorphisms in genes of the renin-angiotensin system and cerebral small vessel disease.

BACKGROUND: Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). METHODS: 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene. RESULTS: AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024). CONCLUSIONS: RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.

Angiotensinogen↗
PubMed2004

Endothelial nitric oxide gene haplotypes and risk of cerebral small-vessel disease.

BACKGROUND AND PURPOSE: Genetic influences are important in multifactorial cerebral small-vessel disease (SVD) and may act via endothelial dysfunction. Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) is a key mediator of endothelial function. We determined the role of 3 potentially functional eNOS polymorphisms (T-786C, intron 4ab, G894T) located toward the 5' flanking end of the gene as risk factors for SVD and different SVD subtypes: isolated lacunar infarction (n=137) and ischemic leukoaraiosis (n=160). METHODS: Three hundred patients with SVD and 600 community controls were studied. Genotypes were determined through polymerase chain reaction with or without restriction fragment digestion. Nitrate (NO(x)) levels were determined in a subgroup by use of a Griess method. Polymorphisms were tested individually and in combination with haplotype analysis. RESULTS: The intron 4a variant was protective against SVD. This effect was confined to isolated lacunar infarction (odds ratio, 0.55; 95% confidence interval, 0.35 to 0.86; P=0.01). Haplotypes encountered were significantly different in this subtype compared with controls (P=0.001), with the -786C promoter/intron 4a combination particularly underrepresented. NO(x) levels were associated with the T-786C locus (P=0.03) but only in the presence of the intron 4a allele (P=0.07 for interaction). CONCLUSIONS: The intron 4ab insertion/deletion genotype was associated with isolated lacunar infarction. Haplotype and functional studies suggested that the protective effect of the 4a variant could be mediated through changes in eNOS promoter activity and increased NO levels. The specific association with isolated symptomatic lacunar infarction and not ischemic leukoaraiosis may reflect different etiopathogeneses of the 2 subtypes. Lack of NO could predispose to localized microatheroma in proximal arterioles rather than diffuse arteriosclerosis affecting distal perforating vessels.

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