Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10−94; GT: OR = 15.87, p = 2.62 × 10−9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10−108; GT: OR = 12.63, p = 3.44 × 10−64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
Abstract. Orientia tsutsugamushi induces vasculitis leading to symptoms of systemic organ invasion including meningitis and meningoencephalitis. We conducted a retrospective case-control study of scrub typhus patients to investigate the clinical and laboratory features of patients with scrub typhus meningitis or meningoencephalitis, and the therapeutic outcomes, and to determine the predictor factors. Cases were 22 patients with scrub typhus meningitis or meningoencephalitis, and controls were 303 patients without meningitis or meningoencephalitis. Multivariate analysis showed that the presence of pneumonitis was associated with the occurrence of scrub typhus meningitis and meningoencephalitis (odds ratio [OR] 8.9; P 0.001; confidence interval [CI] 2.9-27.2). Although appropriate antimicrobials such as doxycycline agents were administered at an early stage, meningitis or meningoencephalitis still occurred in some cases. Physicians should be aware that meningitis or meningoencephalitis may develop during appropriate drug therapy such as doxycycline. Close observation and great care are essential for patients with risk factors, particularly pneumonitis.
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