Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/30/2010
Publication Date: 6/18/2010
Citation: Belisle, S.E., Hamer, D.H., Leka, L.S., Dallal, G.E., Delgado-Lista, J., Fine, B.C., Jacques, P.F., Ordovas, J.M., Meydani, S.N. 2010. IL-2 and IL-10 gene polymorphisms are associated with respiratory tract infection and may modulate the effect of vitamin E on lower respiratory tract infections in elderly nursing home residents. American Journal of Clinical Nutrition. 92:106-114. Interpretive Summary: With age, the body is less able to fight off infections. Vitamin E supplements have been suggested to improve the body’s ability to fight off infection. Not all elderly individuals that take vitamin E supplements have the same improvement in response to infection. Other researchers have shown that genetic differences between people influence immune response and risk of infection. Further, researchers have shown that the effect of nutrients on health may depend on genetic differences. We tested if people with common genetic differences had different number of respiratory infections and if these common genetic differences explained why the effect of vitamin E on infection varied from person to person in the elderly. To test this, we used information on infection, baseline health information, and genetic background from a group of elderly people who were given vitamin E supplements for one year and a group given a placebo for a year. We looked specifically at genetic differences at genes that make the immune proteins named IL-1beta, IL-6, IL-10, IL-2, IFN-gamma and TNF-alpha. We observed that common genetic differences located at the cytokines named IL-10 and IL-2 may influence the risk of respiratory infection in those elderly people. We also observed that a common genetic difference at IL-10 may influence the response to vitamin E in those elderly people, particular in women. Overall, these observations indicate the risk of infection and the effect of vitamin E on respiratory infections in elderly people may be influenced by common genetic differences. The information from our study adds to the body of knowledge that will eventually help us determine why vitamin E does not affect all people the same way. Given the risk of illness that comes with aging, such knowledge will help us determine which elderly people might benefit the most in strengthening their immune systems from taking vitamin E supplements.
Technical Abstract: Vitamin E supplementation has been suggested as a potential strategy to prevent respiratory infections (RI) in the elderly. Previously, we showed that vitamin E reduced RI in some but not all nursing home residents. The efficacy of vitamin E supplementation may depend on individual factors including specific single nucleotide polymorphisms (SNPs) at immunoregulatory genes. We examined whether a vitamin E-gene interaction might explain individual responses to vitamin E for protection from RI. Data and DNA from a previous vitamin E intervention study (200 IU vitamin E or placebo daily for 1-year) in elderly nursing home residents were used to examine vitamin E-gene interactions for incidence of RI. The genotype of common SNPs at interleukin (IL)-1beta, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma genes was determined in 500 study participants. Negative binomial regression was used to analyze the association between genotype and incidence of infection. This trial has been registered with Clinicaltrials.gov (identifier: #NCT00758914). The effect of vitamin E on lower RI depended on gender and IL-10 -819G>A (P=0.03 for interaction lower RI). Furthermore, we observed that IL-2 -330A>C (P=0.02 for upper RI), IL-10 -819G>A (P=0.08 for upper RI) and IL-10 -1082C>T (P<0.001 for lower RI in men) were associated with respiratory infections independent of vitamin E. Genetic factors and gender should be considered in future studies of vitamin E and lower respiratory infection. Common SNPs at cytokine genes may be linked to individual risk of respiratory infection in the elderly.