APOA-IV POLYMORPHISM ASSOCIATED WITH MYOCARDIAL-INFARCTION IN OBESE NIDDM PATIENTS - THE SAN-LUIS VALLEY DIABETES STUDY

Non-insulin-dependent diabetes mellitus (NIDDM) confers myocardial inf arction (MI) risk unexplained by known factors. In 356 NIDDM patients and 1,087 people with normal glucose tolerance, we investigated the as sociation between MI risk and polymorphism at codon 360 in the apolipo protein A-IV (apoA-IV) gene. During 1984-1992, MI was diagnosed in 84 diabetic and in 106 nondiabetic people. The risk of MI did not differ by apoA-IV phenotype in nondiabetic people; however, in NIDDM patients , those with the apoA-IV 1-2 phenotype had 2.8 (95% confidence interva l: 1.4-5.6) higher MI risk than those with the 1-1 phenotype, adjustin g for age, gender, ethnicity, hypertension, smoking, body mass index, fat centrality, and low-density lipoprotein and high-density lipoprote in cholesterol. The risk of MI was particularly high in obese NIDDM pa tients with the apoA-IV 1-2 phenotype: 5.1 (2.4-11.2) times that in ob ese apoA-IV 1-1 NIDDM patients and 7.7 (3.6-16.7) times that in lean n ondiabetic people. The effect of apoA-IV 1-2 did not appear to be a pa rt of the insulin-resistance syndrome nor was it dependent on diabetes duration or control. One half of the excess MI risk in the diabetic p opulation studied was explained by the apoA-IV 1-2 phenotype. These re sults indicate that similar to 17% of NIDDM patients have a high MI ri sk apoA-IV phenotype that is particularly deleterious in obese patient s.