两个APOL1基因变体与肾病有关

African-Americans with two copies of the APOL1 gene have about a 4 percent lifetime risk of developing a form of kidney disease, according to scientists at the National Institutes of Health. The finding brings scientists closer to understanding why African-Americans are four times more likely to develop kidney failure than whites, as they reported in the Oct. 13 online edition of the Journal of the American Society of Nephrology. Researchers including Jeffrey Kopp, M.D., at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases and Cheryl Winkler, Ph.D, of the National Cancer Institute have begun tracing the effects of having two variants of the APOL1 gene, which occurs in about 12 percent of African-Americans.

Researchers earlier linked this gene to susceptibility for kidney disease. When a person has kidney disease, the kidneys are unable to fully remove waste products and extra water from the blood. The researchers studied a common kidney disease called focal segmental glomerulosclerosis（肾小球硬化症） (FSGS), which often progresses to end-stage kidney disease and the need for dialysis or a kidney transplant. The researchers studied FSGS patients who came to the NIH Clinical Center or other collaborating medical centers, and who provided blood samples for genetic studies.

"These findings explain nearly all of the excess risk of non-diabetic kidney failure in African-Americans. African-Americans with no variant or one variant have about the same risk of end-stage kidney disease as their white counterparts," Winkler said. "People with two APOL1 variants have greatly increased risk of particular kidney diseases -- by 17- to 30-fold."

The researchers found that African-Americans with two copies of the APOL1 variants have about a 4 percent lifetime risk of developing FSGS. Those who develop kidney disease tend to do so at younger ages than other FSGS patients, with 70 percent diagnosed with FSGS between age 15 and 39, compared to 42 percent in that age group for people with one or no APOL1 variants.

Possessing two APOL1 variants also raises the risk for African-Americans with HIV of developing HIV-associated nephropathy（肾病） (HIVAN) -- a type of kidney disease that develops in some people with human immunodeficiency virus -- to 50 percent among those not getting anti-viral therapy. Anti-viral therapy appears fairly effective at preventing HIVAN.