• Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

      Dodani, Sunita; Dong, Yanbin; Zhu, Haidong; George, Varghese; Department of Medicine (2010-03-19)
      Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.
    • Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk?

      Dodani, Sunita; Department of Medicine (2009-02-02)
      BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. DISCUSSION: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. CONCLUSIONS: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.