Objective: Investigate the distribution and characteristics of 5'pentanucleotide TTTTA repeat (PNTR) polymorphism of apolipoprotein (a) [apo (a)] gene among Chinese patients with myocardial infarction (MI) and cerebral infarction, and its relationship to plasma lipoprotein (a) [Lp (a)] level.
Methods: DNA was extracted from the peripheral blood of 438 patients with myocardial infarction (MI, documented angiographically) and 218 controls, and 809 patients with cerebral infarction (documented by CT) and 1 817 controls. Plasma Lp (a) level was measured by ELISA. PNTR polymorphism of apo (a) gene was determined by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis.
Results: Eight alleles and 29 genotypes in apo (a) PNTR were detected in the four groups. The frequency of (TTTTA)(4 - 7) allele in the cerebral infarction group was 7.0%, significantly higher than that in control group (5.4%, P < 0.05). The frequency of genotype (TTTTA)(5/8) in MI group was 13.2%, significantly higher than that in the control group (7.8%, P < 0.05). No significant difference was seen in other alleles and genotypes among different groups (all P > 0.05). The level of triglyceride (TG) in patients with MI was 5.13 mmol/L +/- 1.15 mmol/L, significantly higher than that in controls (4.90 mmol/L +/- 0.99 mmol/L, P < 0.05). The level of TG in patients with cerebral infarction was 1.84 mmol/L +/- 1.36 mmol/L, not significantly different from that in controls (1.83 mmol/L +/- 1.51 mmol/L). The level of total cholesterol (TC) in patients with MI was 4.85 mmol/L +/- 1.04 mmol/L, significantly lower than that in controls (4.97 mmol/L +/- 1.00 mmol/L, P < 0.001). The level of TC in patients with cerebral infarction was 1.97 +/- 1.11 mmol/L, not significantly different from that in controls (1.79 mmol/L +/- 1.23 mmol/L). A negative correlation between the number of PNTR and Lp (a) level was observed in both MI group (P < 0.001) and cerebral infarction group (P < 0.01), and not in the control group. Small fragment repeat of apo (a) PNTR was correlated with cerebral infarction (OR = 1.4, 95% CI: 1.040 approximately 1.910), not significantly with MI (P > 0.05). Multiple logistic regression analysis showed that individuals with plasma Lp (a) > 300 mg/L had higher risk of MI (OR = 2.4, 95% CI: 1.630 - 3.594), and a higher risk of cerebral infarction (OR = 1.6, 95% CI: 1.013 - 2.021) after adjustment for age, sex, SBP, DBP, BMI, smoking, TC, TG, HDL-C, LDL-C and Glu.
Conclusion: Plasma Lp (a) is an independent risk factor for MI and cerebral infarction. PNTR of apo (a) gene was negatively correlated with Lp (a) levels both in MI group and cerebral infarction group. Association with PNTR genotype was only found in cerebral infarction, but not in MI.