Association of interleukin-4 genetic polymorphisms with sporadic Alzheimer's disease in Chinese Han population.
Cytokine interleukin-4 (IL-4) is thought to play a role in the pathogenesis of Alzheimer's disease (AD). This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNP) of IL-4 gene and AD susceptibility. This case-control study was conducted in Chinese Han populations consisting of 203 AD patients and 205 controls. Three common SNPs of IL-4 gene, including -590C>T (rs2243250), -33C>T (rs2070874), and -1098T>G (rs2243248), were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data show that -590C and -1098G alleles of IL-4 were more common in AD patients (30.5% vs 22.2% p=0.007; 14.3% vs 3.4% p<0.0001) and significantly associated with elevated risk for AD (OR=1.51 95% CI 1.05-2.23; OR=4.78 95% CI 2.37-7.67). Haplotype analysis revealed five common haplotypes CCG (OR=4.41), CCT (OR=1.22), TTT (OR=1.02), CTT (OR=0.7), and TCT (OR=0.14), from highest to lowest risk for AD. None of the associations appeared to be modified by APOE ɛ4 genetic variant. Bioinformatic analysis shows that -590C>T and -1098T>G have a linkage disequilibrium (LD) with multiple potentially functional SNPs inside IL-4 gene. Our findings indicate that the -590C and -1098G alleles located in the promoter of IL-4 may increase the susceptibility to AD among the Han Chinese and might be used as molecular markers for AD risk evaluation.
Department of Geriatric Neurology, Nanjing Medical University Affiliated to Nanjing Brain Hospital, Nanjing, Jiangsu 210029, People's Republic of China.
Wei
W
Li
Clinical Laboratory, Nanjing Medical University Affiliated to Nanjing Brain Hospital, Nanjing, Jiangsu 210029, People's Republic of China.
Xiaohua
X
Qian
Department of Geriatric Neurology, Nanjing Medical University Affiliated to Nanjing Brain Hospital, Nanjing, Jiangsu 210029, People's Republic of China.
Hong
H
Teng
Department of Science and Education, Nanjing Medical University Affiliated to Nanjing Brain Hospital, Jiangsu 210029, People's Republic of China.
Ying
Y
Ding
Department of Geriatric Neurology, Nanjing Medical University Affiliated to Nanjing Brain Hospital, Nanjing, Jiangsu 210029, People's Republic of China. Electronic address: zhangli_nbh@163.com.
Li
L
Zhang
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D044466:Asian People; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015847:Interleukin-4
Alzheimer's disease; Han Chinese; IL-4; Linkage disequilibrium; Single nucleotide polymorphisms