Sunlight can worsen rashes and even trigger a flare-up of the disease in some people with lupus. It is well known that sun-sensitive lupus patients carry certain variants of the HLA genes, but those are not the ones that piqued the interest of Patricia Fraser, a molecular epidemiologist at Harvard Medical School. "Our hypothesis was that sun exposure causes damage to cells in such a way that it releases damaged DNA or damages the DNA itself," says Fraser. According to Fraser's scheme, the body recognizes the damaged DNA as foreign, and this generates an autoimmune reaction to the molecule. This would explain the presence of anti-DNA antibodies, a cardinal sign of lupus.

"We also knew that several members of the glutathione S-transferase (GST) family of enzymes were active in modulating damage to DNA by UV light," she adds. However, there are genetic polymorphisms of these enzymes that alter their functions. In particular, the "null" variant of the GSTM1 gene does not signal cells to make the GASTM1 enzyme. "Theoretically, people who are homozygous for the GASTM1 null variant have reduced ability to compensate for toxic exposures, such as UV light," says Fraser.

Indeed, that turned out to be true. "People with 24 or more months of occupational sun exposure who are homozygous for the GSTM1 null gene are about three times more likely to develop lupus compared to people with the same sun exposure, who do not carry the gene," Fraser says (P.A. Fraser et al., "Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity," J Rheumatol , 30:276-82, 2003.). It is interesting that the association was found only in Caucasians, not African-Americans, but Fraser does not know why.