Interaction between interleukin-8 and methylenetetrahydrofolate reductase genes modulates Alzheimer's disease risk.
OBJECTIVE
Interleukin-8 (IL-8), a potent chemoattractant for neutrophils, has been implicated in the pathogenesis of Alzheimer's disease (AD). The ability of individuals to produce high levels of IL-8 is partially determined by the IL-8 -251 T/A polymorphism. Therefore, we investigated the association between this polymorphism and AD in a Chinese population. Additionally, in light of the stimulatory effect of homocysteine on the production of IL-8, we also sought to determine whether the methylenetetrahydrofolate reductase (MTHFR) gene 677 C/T variant, a genetic modifier of the serum homocysteine level, may interact with the IL-8 -251 polymorphism in determining the AD risk.


METHODS
Genotyping of 198 AD patients and 240 matched controls was performed by PCR-RFLP.


RESULTS
The presence of the MTHFR 677 C/T and 677 T/T genotypes conferred a marginally significant increase in the risk for AD (OR = 1.666, 95% CI = 1.022-2.715, and OR = 1.892, 95% CI = 1.124-3.187) and the presence of the IL-8 -251 polymorphism was not associated with AD. However, the OR for AD associated with joint occurrence of the MTHFR 677 T/T and the IL-8 -251 A/A genotypes was 2.512 (95% CI = 1.151-5.483).


CONCLUSIONS
Our data suggest a critical role for IL-8/MTHFR interactions in the development of AD.
Li
Keshen
K
Laboratory of Biochemistry and Molecular Biology, Harbin Engineering University, Harbin, China.
Liu
Shengyuan
S
Yao
Songpo
S
Wang
Binyou
B
Dai
Dawei
D
Yao
Lifen
L
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
D016209:Interleukin-8; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)