Affiliations: [a] Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Palermo, Italy | [b] Unità Operativa di Immunoematologia e Medicina Trasfusionale, AOUP “Paolo Giaccone”, Università di Palermo, Palermo, Italy | [c] Istituto di Biomedicina ed Immunologia Molecolare (IBIM), CNR, Palermo, Italy | [d] Dipartimento Biomedicina Sperimentale e Neuroscienze Cliniche, Università di Palermo, Palermo, Italy
Correspondence:
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Correspondence to: Prof. Calogero Caruso, MD, Dipartimento di Biopatologia e Biotecnologie mediche e Forensi, Università di Palermo, Corso Tukory, 211, 90134 Palermo, Italy. Tel.: +39 0916555911; Fax: +39 091 23860793; E-mail: [email protected].
Abstract: It has been hypothesized that polymorphisms of interleukin (IL)-10 genes affect the risk of developing late onset Alzheimer's disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the IL-10 gene with AD risk. Fifteen studies investigating the association between IL-10 polymorphisms (-1082, -819, -592) and AD were found and analyzed. The model-free approach was applied to meta-analyze these case-control genetic association studies. Available data suggested an association between -1082 polymorphism and AD risk with a marginal statistical significance (GG versus AG/AA: pooled odds ratio [OR]: 0.82, 95% confidence interval CI: 0.65–1.02) and evidence of a moderate degree of between-study heterogeneity (χ2 = 27.13, d.f. = 13, p = 0.01, I2 = 52%). For the -819 and -592 polymorphisms, we did not find an association with AD, but significant between-study heterogeneity made genotype data pooling unacceptable. Analysis by IL-10 haplotype showed that the -1082G/-819C/-592C haplotype is associated with a lower risk of AD, although with a marginal statistical significance, probably due to the low number of studies included (GCC versus other genotypes: OR: 0.61, 95% CI: 0.32–1.15; I2: 85%). Current findings suggest a possible association between -1082 A > G polymorphism and the risk of developing AD; this effect is more evident in the oldest patients. The high degree of between-study heterogeneity, due to several underpowered studies and to other methodological problems of individual studies underlies the need for further methodologically adequate studies.
