Population characteristics
The 1,966 individuals in this study, ages between 20 and 99 years, consisted of 938 CI patients (581 males and 357 females) and 1,028 individuals with non-CI (622 males and 406 females) as controls. As shown in Table 1, the average age of the CI patients was 65.6±10.6 years, with 63.9±9.9 years for males and 68.3±11.2 years for females. The average age of the controls was 63.7±12.4 years, with 62.9±12.6 years and 64.8±12.1 years for males and females, respectively. There were statistically significant differences in percentage of smokers (P<0.001), prevalence of hypertension (P<0.001) and TG level (P<0.001) between the patients and controls, though there were no statistically significant differences in age, TC, HDL-C, LDL-C, Apo-A1, Apo-B, Apo-A1/Apo-B or percentage of alcohol cases. The differences in prevalence of hypertension (P<0.001) and TG (P=0.003) levels between female patients and female controls were also statistically significant, and prevalence of hypertension (P<0.001) and TG (P=0.009) were significant among males.
Genotype and haplotype frequencies of APOE gene
Among all subjects, the frequencies of genotypes ɛ3/ɛ3, ɛ3/ɛ4, ɛ2/ɛ3, ɛ2/ɛ4, ɛ4/ɛ4, and ɛ2/ɛ2 were 73.60%, 13.33%, 9.87%, 1.58%, 1.07%, and 0.56%, respectively. The frequencies of alleles ɛ3, ɛ4 and ɛ2 were 85.20%, 8.52%, and 6.28% respectively. As the results showed, ɛ3/ɛ3 was the most common APOE genotype, and ɛ3 was the allele with the highest frequency, followed by ɛ4 and ɛ2 (Table 2).
There were statistically significant differences in genotype ɛ2/ɛ2 (c2=3.866, P=0.049), ɛ2/ɛ3 (c2=20.030, P<0.001), ɛ3/ɛ4 (c2=16.960, P<0.001), and ɛ4/ɛ4 (c2=4.786, P=0.029) in the patients compared with the controls. The frequencies of genotypes ɛ2/ɛ3 (c2=14.579, P<0.001) and ɛ3/ɛ4 (c2=15.177, P<0.001) between male patients and male controls showed statistically significant differences; in contrast, a significant difference only in genotype ɛ2/ɛ3 (c2=5.744, P=0.017) was detected among females (Patients vs Controls=6.16% vs 11.08%). The frequencies of allele ɛ2 (c2=18.682, P<0.001) and ɛ4 (c2=25.516, P<0.001) showed statistically significant differences in the patients compared with controls, including between male patients and male controls and between female patients and female controls, respectively (Table 2).
Genotype and haplotype frequencies of SLCO1B1 gene
The frequencies of genotypes *1b/*1b, *1a/*1b, *1b/*15, *1a/*15, *1a/*1a, *15/*15, and *1a/*5 were 41.40%, 32.50%, 13.48%, 5.95%, 5.44%, 1.17%, and 0.05%, respectively, in all subjects. The corresponding frequencies in the cerebral infarction patient group were 38.70%, 33.69%, 13.75%, 6.72%, 5.86%, 1.17%, and 0.11%. And 43.87%, 31.42%, 13.23%, 5.25%, 5.06%, 1.17%, and 0% in the control group. There was no statistically significant difference in the frequencies of these genotypes in the patients compared with the controls. The frequencies of SLCO1B1 genotypes between male patients and male controls were not significantly different, nor were those in the female subjects (Table 3).
Four haplotypes of the two SNPs of SLCO1B1 were analysed. The *1b (388G-521T) haplotype (64.39%) presented the highest frequency, followed by haplotype *1a (388A-521T) (24.69%), *15 (388G-521C) (10.89%) and *5 (388A-521C) (0.03%) haplotypes. The frequencies of SLCO1B1 haplotypes between male patients and male controls and between female patients and female controls showed no statistically significant differences (Table 3).
Relationships between serum lipid level and APOE allele and logistic regression analysis of the risk of ε4 allele for CI
Relationships between APOE alleles (ε2, ε3, and ε4) and serum lipid level were analysed. Subjects with the APOE ε2/ε4 genotype (n=31) were excluded because ε2 and ε4 alleles play opposing roles in lipid metabolism. In this study, ε4 carriers had significantly higher LDL-C and Apo-B and lower Apo-A1/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. There were no significant impacts of APOE polymorphism on the TG, TC, HDL-C and Apo-A1 levels (Table 4).
Logistic regression analysis was performed to determine independent predictors for CI (Table 5), and the results indicated significantly higher risks of CI in the presence of high LDL-C (OR 1.524, 95% CI 1.092-2.100, P=0.013), and high ApoB (OR 3.046, 95% CI 1.188-7.809, P=0.020), smoking (OR 1.459, 95% CI 1.166-1.825, P=0.001), hypertension (OR 2.599, 95% CI 2.136-3.164, P<0.001), and the ε4 allele (OR 1.822, 95% CI 1.390-2.388, P<0.001).