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

Magalhães, Carolina Antunes; Carvalho, Maria das Graças; Sousa, Lirlândia Pires de; Caramelli, Paulo; Gomes, Karina Braga

doi:10.1590/0004-282X20170110

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VIEWS AND REVIEWS • Arq. Neuro-Psiquiatr. 75 (9) • Sept 2017 • https://doi.org/10.1590/0004-282X20170110 copy

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

A doença de Alzheimer e os polimorfismos no gene da citocina IL-10: há alguma associação?

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Alzheimer’s disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

Alzheimer’s disease; inflammation; Interleukin-10

Authors	Location	Groups	IL-10 polymorphism(s)	Conclusion
Depboylu et al.,⁴⁰ 2003	Germany	AD: 406 Control: 251	-1087A/G	No significant differences have been found between AD patients and controls.
			-824C/T
			-597C/A
Lio et al.,⁴¹ 2003	Italy	AD: 132 Control: 213	-1082A/G	The presence of -1082A allele associated with a low production of IL-10, may be considered as an additive and independent genetic risk factor for AD.
			-819C/T
			-592C/A
Scassellati et al.,⁴ 2004	Italy	AD: 215 Control: 153	-1082G/A	Haplotype frequencies did not reveal differences. However, the genotype GCC/ACC was more frequent in AD.
			-819C/T
			-592C/A
Arosio et al.,⁴³ 2004	Italy	AD: 65 Control: 65	-1082A/G	In AD there was a significant increase of the -1082A allele and a decrease of -1082GG genotype frequencies.
			-819C/T
			-592C/A
Ma et al.,⁴⁶ 2005	China	AD: 95 Control: 117	-1082A/G	The reduced expression of IL-10 was associated with the -819C and -592C alleles.
			-819C/T
			-592C/A
Culpan et al.,³⁹ 2006	England	AD: 160 Control: 92	-3538T/A/-1354G/A	None of the SNPs found to be associated with AD.
			-1082A/G/-819C/T
			-592C/A
Ramos et al.,⁴⁸ 2006	America	AD: 265 Control: 347	-1082A/G	No difference was observed between AD patients and controls.
Ramos et al.,⁴⁸ 2006	America	AD: 265 Control: 347	-592C/A
Bagnoli et al.,⁴⁵ 2007	Italy	AD: 222 Control: 179	-1082A/G	Haplotype -1082A/-819T was associated with an increase in the risk of developing AD.
Bagnoli et al.,⁴⁵ 2007	Italy	AD: 222 Control: 179	-819C/T
Vural et al.,⁴⁹ 2009	Turkey	AD: 101 Control: 138	-1082A/G	Heterozygous (AG) or A allele carriers (AG+AA genotype) were associated with approximately two-fold increase in the risk of AD.
Combarros et al.,²⁵ 2009	England, Spain, Netherland and Germany	AD: 1. 757 Control: 6. 295	-1082A/G	Dysregulation of the IL-10 gene contributes to chronic low-grade inflammation in some elderly people and increases the risk of AD.
Arosio et al.,⁴⁴ 2010	Italy	MCI: 138 AD and Control: Arosio et al., 2004	-1082A/G	The allele frequencies of this SNP in a-MCI subjects were similar to those of AD patients, whereas those of mcd-MCI were comparable to controls.
Ribizzi et al.,⁵⁰ 2010	Caucasian population	AD: 19 Control: 20	-1082A/G	The -819C allele was raised in AD group and associated with low producers of IL-10.
Ribizzi et al.,⁵⁰ 2010	Caucasian population	AD: 19 Control: 20	-819C/T
Moraes et al.,⁴² 2013	Brazil	AD: 120 Control: 412	-1082A/G	The SNP -1082A/G exhibited an effect in predisposition to the onset of AD. Almost 40% lower chance of AD among homozygotes of the IL10 -1082A allele.
Kang et al.,⁵³ 2015	Korea	AD: 86 No AD: 625	-1082A/G	No significant association between AD patients and No AD patients.
Vargas-Alarcón et al.,⁵⁴ 2016	Mexico	AD: 122	-1082A/G	Identified two risk haplotypes (ATA and CTA) and four protection haplotypes (ATG, CTG, ACG and CCG).
		Vascular dementia: 67	-819C/T
		Mixed dementia: 32
		Control: 986
Fraga et al.,⁵⁶ 2016	Brazil	Cognitive impairment: 135	-1082A/G	Haplotype -1082/-819/-592, associated with lower expression of IL-10 were more frequent in patient group.
		Control: 124	-819C/T
			-592C/A

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[1] Correspondence: Karina Braga Gomes; Faculdade de Farmácia da UFMG; Avenida Antônio Carlos, 6627; 31270-901 Belo Horizonte MG, Brasil; E-mail: karinabgb@gmail.com