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Abstract
Background
The association of apolipoprotein E (apoE) polymorphism with interindividual variability of serum lipid concentrations and the initiation and progression of atherosclerosis is inconclusive. This study was performed to explore the associations of apoE with lipid concentrations and ischemic stroke in patients with large artery atherosclerosis (LAA) subgroup or without atherosclerotic vascular lesions (small artery occlusion, SAO) subgroup through a case-control study among the Korean population.
Methods
The ischemic stroke group (n=194) was subdivided into an LAA subgroup (n=112) and a SAO without atherosclerotic lesion subgroup (n=82). An age-matched healthy control group (n= 168) was recruited. Serum lipid concentrations were measured and apoE genotypes were determined by real-time PCR and melting curve analysis with the LightCycler (Roche Diagnostics).
Results
The frequency of the ε4 carriers was significantly higher in the ischemic stroke group (22.7%) than in the control group (11.9%) (P=0.01). However, the frequency of ε4 carriers showed no difference between the LAA and SAO subgroups (22.3% vs 23.2%, P=0.89). The adjusted low density lipoprotein cholesterol (LDLc) concentration was significantly higher in ischemic stroke group than in control group (P=0.04), but showed no significant differences in all lipid concentrations between the LAA and SAO subgroups. LDLc concentrations were lower in ε2 carriers than in ε3 and ε4 alleles, but showed no difference between the ε4 carriers and ε3 allele.
Conclusions
Although there was an association between the ε4 allele and ischemic stroke and between the LDLc concentration and ischemic stroke, there was no significant difference in the lipid concentrations and distribution of apoE genotypes between the LAA and SAO subgroups. Therefore, the ε4 allele may have different effects on the ischemic stroke that are independent of the atherosclerotic mechanism by high LDLc concentration.
References
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Table 1.
Distribution of apoE genotypes and serum lipid concentrations in the control group and the ischemic stroke group
| Characteristics | Control group | Stroke group | P* |
|---|---|---|---|
| Number | 168 | 194 | |
| Sex (M:F) | 94:74 | 116:78 | 0.46 |
| Age | 62.3 (±6.3) | 62.0 (±9.5) | 0.66 |
| Genotype† | |||
| ε2/ε2 | 2 (1.2%) | 0 (0.0%) | 0.13 |
| ε2/ε3 | 18 (10.7%) | 24 (12.4%) | 0.62 |
| ε3/ε3 | 128 (76.2%) | 126 (64.9%) | 0.02 |
| ε3/ε4 | 19 (11.3%) | 44 (22.7%) | 0.00 |
| ε4/ε4 | 1 (0.6%) | 0 (0.0%) | 0.28 |
| Carrier† | |||
| ε2 carrier | 20 (11.9%) | 24 (12.4%) | 0.89 |
| ε3 carrier | 128 (76.2%) | 126 (64.9%) | 0.03 |
| ε4 carrier | 20 (11.9%) | 44 (22.7%) | 0.01 |
| Lipid profile‡ | |||
| Cholesterol (mg/dL) | 193.5 (187.3–199.7) | 199.9 (194.3–205.6) | 0.19 |
| Triglyceride (mg/dL) | 148.3 (132.7–163.9) | 146.0 (131.9–160.2) | 0.85 |
| HDLc (mg/dL) | 44.5 (42.4–46.7) | 42.1 (40.2–44.0) | 0.15 |
| LDLc (mg/dL) | 119.3 (113.5–125.0) | 128.6 (123.4–133.9) | 0.04 |
* Two sample t-test for continuous variables and chi-square test for nominal variables between the control group and the ischemic stroke group;
† Significant differences in distribution of apoE genotype and apoE carrier between the control group and the ischemic stroke group (χ2=12.0, 4 d.f., P=0.02 and χ2=6.7, 2 d.f., P=0.04, respectively);
Table 2.
Distribution of apoE genotypes and serum lipid concentrations in the LAA subgroup and the SAO subgroup
| Characteristics | LAA | SAO | P* |
|---|---|---|---|
| Number | 112 | 82 | |
| Sex (M:F) | 67:45 | 49:33 | 1.00 |
| Age | 63.2 (±8.6) | 60.2 (±10.5) | 0.03 |
| Hypertension | 68 (60.7%) | 52 (63.4%) | 0.77 |
| Diabetes | 34 (30.4%) | 18 (22.0%) | 0.25 |
| Smoker | 10 (8.9%) | 6 (7.3%) | 0.80 |
| Genotype† | |||
| ε2/ε2 | 0 (0.0%) | 0 (0.0%) | |
| ε2/ε3 | 11 (9.8%) | 13 (15.9%) | 0.21 |
| ε3/ε3 | 76 (67.9%) | 50 (61.0%) | 0.32 |
| ε3/ε4 | 25 (22.3%) | 19 (23.2%) | 0.89 |
| ε4/ε4 | 0 (0.0%) | 0 (0.0%) | |
| Carrier† | |||
| ε2 carrier | 11 (9.8%) | 13 (15.9%) | 0.21 |
| ε3 carrier | 76 (67.9%) | 50 (61.0%) | 0.32 |
| ε4 carrier | 25 (22.3%) | 19 (23.2%) | 0.89 |
| Lipid profile‡ | |||
| Cholesterol (mg/dL) | 196.4 (189.5–203.3) | 198.5 (190.4–206.6) | 0.70 |
| Triglyceride (mg/dL) | 145.3 (129.8–160.7) | 161.7 (143.6–179.9) | 0.18 |
| HDLc (mg/dL) | 41.0 (38.9–43.0) | 44.1 (41.7–46.5) | 0.05 |
| LDLc (mg/dL) | 126.4 (120.1–132.6) | 122.1 (114.7–129.4) | 0.39 |
* Two sample t-test for continuous variables and chi-square test for nominal variables between the LAA subgroup and the SAO subgroup;
† No significant differences in distribution of apoE genotype and apoE carrier between the LAA subgroup and SAO subgroup (χ2=13.8, 8 d.f., P=0.09 and χ2=8.4, 4 d.f., P=0.08, respectively);
Table 3.
The comparison of mean lipid concentrations between apoE carriers in the ischemic stroke group and the control group
| Test | ε2 | ε3 | ε4 | P* | ε2 vs. ε3 | ε2 vs. ε4 | ε3 vs. ε4 | |
|---|---|---|---|---|---|---|---|---|
| Total (n=362) | N | 44 | 253 | 65 | ||||
| TC (mg/dL) | 191.0 (181.1–200.8) | 197.0 (192.9–201.1) | 200.7 (192.6–208.7) | 0.32 | 0.80 | 0.40 | 1.0 | |
| TG (mg/dL) | 171.3 (146.7–195.9) | 141.4 (131.2–151.6) | 152.9 (132.8–173.0) | 0.07 | 0.09 | 0.77 | 0.95 | |
| HDLc (mg/dL) | 45.1 (41.7–48.4) | 43.4 (42.0–44.8) | 41.3 (38.5–44.1) | 0.22 | 1.0 | 0.28 | 0.56 | |
| LDLc (mg/dL) | 111.6 (102.5–120.8) | 125.3 (121.5–129.1) | 128.8 (121.3–136.3) | 0.01 | 0.02 | 0.01 | 1.0 | |
| Control (n=168) | N | 20 | 127 | 21 | ||||
| TC (mg/dL) | 186.7 (174.3–199.2) | 197.9 (193.0–202.7) | 197.9 (185.9–210.0) | 0.26 | 0.31 | 0.61 | 1.0 | |
| TG (mg/dL) | 167.9 (130.8–205.1) | 135.9 (121.3–150.5) | 147.4 (111.6–183.2) | 0.27 | 0.35 | 1.0 | 1.0 | |
| HDLc (mg/dL) | 41.8 (36.6–46.9) | 45.1 (43.0–47.1) | 42.1 (37.1–47.1) | 0.34 | 0.74 | 1.0 | 0.85 | |
| LDLc (mg/dL) | 111.3 (99.2–123.5) | 125.6 (120.8–130.3) | 126.3 (114.6–138.0) | 0.09 | 0.1 | 0.24 | 1.0 | |
| SAO (n=82) | N | 13 | 50 | 19 | ||||
| TC (mg/dL) | 188.0 (167.0–209.0) | 195.9 (185.2–206.7) | 213.4 (195.7–231.1) | 0.14 | 1.0 | 0.21 | 0.31 | |
| TG (mg/dL) | 195.6 (141.5–249.7) | 158.6 (131.0–186.2) | 148.5 (102.9–194.0) | 0.38 | 0.69 | 0.56 | 1.0 | |
| HDLc (mg/dL) | 46.1 (39.6–52.6) | 43.5 (40.2–46.9) | 44.8 (39.3–50.2) | 0.77 | 1.0 | 1.0 | 1.0 | |
| LDLc (mg/dL) | 102.8 (84.6–120.9) | 120.7 (111.4–130.0) | 139.0 (123.7–154.2) | 0.01 | 0.26 | 0.01 | 0.15 | |
| LAA (n=112) | N | 11 | 76 | 25 | ||||
| TC (mg/dL) | 200.3 (178.0–222.5) | 195.8 (187.3–204.2) | 195.8 (180.9–210.7) | 0.93 | 1.0 | 1.0 | 1.0 | |
| TG (mg/dL) | 148.8 (105.0–192.7) | 138.4 (121.9–155.0) | 163.2 (133.8–192.5) | 0.35 | 1.0 | 1.0 | 0.46 | |
| HDLc (mg/dL) | 49.3 (43.1–55.5) | 40.5 (38.1–42.8) | 38.4 (34.3–42.5) | 0.02 | 0.03 | 0.01 | 1.0 | |
| LDLc (mg/dL) | 121.2 (100.9–141.6) | 127.6 (119.9–135.3) | 124.7 (111.1–138.3) | 0.82 | 1.0 | 1.0 | 1.0 |
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