-174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study.

The aim of this study was to evaluate the association between the -174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and multi-infarct dementia (MID). We studied a group of 122 patients affected by MID and 134 age- and sex-matched controls and evaluated classical risk factors for MID, as well as the distribution of IL-6 alleles and genotypes by polymerase chain reaction and restriction enzyme analysis. The distribution of IL-6 genotypes was 63 GG, 47 GC, 12 CC in patients with MID and 29 GG, 58 GC, 47 CC in control subjects. The GG genotype was significantly more common in the MID group (P<0.0001), while the CC genotype was more common in control patients (P<0.0001). Logistic regression analysis indicated that the presence of GG genotype significantly increases the risk of MID (odds ratio 9.1 [3.1-26.1], P<0.0001). This study indicates a strong association between the -174 G/C polymorphism of the IL-6 gene and MID. Our data support the hypothesis that IL-6 and inflammatory mechanisms are important in the pathophysiology of the vascular changes responsible for cognitive deterioration.

Association between intercellular adhesion molecule-1 E/K gene polymorphism and probable vascular dementia in humans.

Intercellular adhesion molecule-1 (ICAM-1) is implicated in the pathogenesis of ischemic cardiovascular disorders, including cerebral ischemia. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the association between this polymorphism and vascular dementia (VD) by studying 107 patients affected by probable VD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in VD patients than controls (P=0.009). Logistic regression analysis indicated that the presence of the EE genotype significantly increased the risk of VD (odds ratio 3.25, P=0.024). Our findings support the hypothesis that ICAM-1 plays a role in the physiopathology of ischemic cerebrovascular disorders and suggest that genetic polymorphisms of ICAM-1 might be clinically important in the development and progression of neurodegenerative diseases.