Intereleukin-10 Promoter Polymorphism in Mild Cognitive Impairment and in Its Clinical Evolution

Abstract

Specific proinflammatory alleles are associated with higher risk of Alzheimer disease (AD) in different onset age. The homozygosis for the A allele of −1082 polymorphism (G/A) of interleukin-10 (IL-10) promotes a higher risk of AD and reduced IL-10 generation in peripheral cells after amyloid stimulation. In this paper we analysed genotype and allele frequencies of this polymorphism in 138 subjects with mild cognitive impairment (MCI) diagnosed, respectively, as amnestic (a-MCI) and multiple impaired cognitive domains (mcd-MCI). The genotype frequencies were similar in a-MCI and AD subjects, whereas in mcd-MCI comparable to controls (AA genotype: 50% in a-MCI, 49.2% in AD, 28.7% in mcd-MCI and 31.8% in controls). Consequently, both allele and genotype distributions were significantly different between a-MCI and mcd-MCI (allele: P = .02, genotype: P < .05). These results support the theory that polymorphisms of cytokine genes can affect neurodegeneration and its clinical progression. IL-10 may partly explain the conversion of a-MCI to AD or be a genetic marker of susceptibility.

Interleukin-10 Production in Response to Amyloid-β Differs between Slow and Fast Decliners in Patients with Alzheimer’s Disease

“…A study following subjects with mild cognitive impairment (MCI) has shown that MCI converting to AD showed a higher frequency of allele A and −1082AA IL-10 genotype compared with stable MCI or those who convert to vascular dementia suggesting a role of −1082AA polymorphism in converting from MCI to AD [23]. Ex vivo studies confirmed this link between AD and decreased IL-10 production [20,21].…”

“…Despite there being no significant differences in genotype and allele frequencies of -1082 G/A (p = 0.61 and p = 0.33, respectively), -819 C/T and -592 C/A SNPs (p = 0.47 and p = 0.24, respectively), there is a trend toward AD patients having a higher frequency of the low/intermediate IL-10-producing genotypes (−1082 AA/GA: 77%) and lower frequency of −1082GG genotype (23%) compared to controls (65% and 35%, respectively) [19,20,23,25,26]. AD fast showed a lower frequency of high IL-10 producing genotype compared to AD slow (25.0% versus 18.2%).…”

“…To date, −1082AA low IL-10 producer genotype was associated with higher risk of developing AD, whereas −1082GG high IL-10 producer genotype frequency is higher in centenarians [8,[19][20][21][22][23]. A study following subjects with mild cognitive impairment (MCI) has shown that MCI converting to AD showed a higher frequency of allele A and −1082AA IL-10 genotype compared with stable MCI or those who convert to vascular dementia suggesting a role of −1082AA polymorphism in converting from MCI to AD [23].…”

Alzheimer’s disease and cytokine IL-10 gene polymorphisms: is there an association?

“…The allele frequencies of this SNP in a-MCI patients were similar to those of AD patients, whereas those of mcd-MCI patients were comparable to controls. According to the authors, IL-10 may partly explain the conversion of a-MCI to AD, or be a genetic marker of susceptibility 43,44 . In addition, studying the Italian population, Scassellati et al analyzed 215 AD patients and 153 controls.…”

“…They found that the homozygosity for the A allele was associated with a higher risk of AD. The same authors, six years later, analyzed the genotype and allele frequencies of IL-10 -1082A/G polymorphism in 138 patients with MCI diagnosed, respectively, as amnestic (a-MCI) and with multiple impaired cognitive domains (mcd-MCI) in Caucasians from northern Italy 44 . The allele frequencies of this SNP in a-MCI patients were similar to those of AD patients, whereas those of mcd-MCI patients were comparable to controls.…”