Genetics Northern California

Familial Hypoalphalipoproteinemia

Familial hypoalphalipoproteinemia (HA) is a relatively common genetic condition that causes your body to produce low levels of high-density lipoprotein ("good cholesterol”). When you have this inherited disorder you have a higher chance to develop cardiovascular disease, including an added risk for heart attack and stroke.

High-density lipoprotein (HDL)
HDL is made by the liver and the intestines. It is often called “good” cholesterol because it helps lower the risk for cardiovascular disease. HDL moves cholesterol to the liver so it can be removed from the body. HDL also helps the body by reducing inflammation and protecting the walls of the blood vessels from normal wear and tear.

Low HDL levels and apo A-1
Smoking, being overweight, and not exercising can all result in lower HDL levels. However, in familial HA, low levels of HDL are due to a mutation (genetic change) in a gene called apo A-1. Apo A-1 is a protein that is an important part of HDL. When the instruction is not working normally, there are lower levels of HDL in the blood. Mutations in the apo-A1 gene can be inherited from either parent, and in some cases, mutations come from both parents.

There are other things made by the body that influence HDL levels. HDL levels can be affected by mutations in certain enzymes, transport proteins and other lipoproteins involved in making HDL.

Diagnosis
A diagnosis of HA is made by blood tests. HDL is considered low when it reaches a blood level of less than 45 mg/dL for men and less than 50 mg/dL for women.

Treatment
Treatment for people with low HDL levels can include both lifestyle changes and medications. 

Here are some lifestyle strategies that can help improve HDL levels:
   • Focus on healthy fats – see: How fats compare
        o Avoid trans fatty acids
        o Substitute monounsaturated fats for saturated and trans fats
   • Avoid the use of alcohol and cigarettes
   • Exercise regularly, especially aerobic exercise
   • Weight loss, especially weight at the midline, or waist level

There are also medications that can help to increase HDL levels: 
   • Niacin
   • Fibrates (for example, gemfibrozil or fenofibrate)
   • Statins (for example, pravastatin, fluvastatin, lovastatin, simvastatin, atorvastatin, rosuvastatin) can increase or decrease HDL. Individual response may vary, so regular blood tests are recommended.
 
Created by:  Suzanne Kordesh, MPH, RD

References:  
James A. Edwards, The National Lipid Association, www.lipid.org

Low HDL Cholesterol (Hypoalphalipoproteinemia), Vibhuti Singhand Elena Citkowitz,  http://emedicine.medscape.com

Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: A systematic in-depth review.  Eva Boes, Stefan Coassin, Barbara Kollerits, Iris M. Heid, and Florian Kronenberg, Exp Gerontol. 2009 March; 44(3): 136–160.

Reviewed by:  Suzanne Kordesh, MPH, RD,
                      Kimberly Barr, MS, CGC
                      Emily Chen, MD, PhD


Last Reviewed: 5/11/10 
Last Updated: 5/11/10