Wall Street Journal - October 1, 2003
Matt Pottinger, Staff Reporter of The Wall Street Journal

Researchers at Mackay Memorial Hospital in Taipei analyzed genetic samples from SARS patients and healthy people in Taiwan. The study was small and far from conclusive: The researchers themselves view their findings as a starting point for further studies rather than a scientific breakthrough.

But if further research supports their hypothesis, it could lead to a significant advance in scientists' understanding of severe acute respiratory syndrome and how the disease is spread. Confirmation could also potentially lead to genetic screening of doctors and nurses in order to identify those at higher risk and steer them away from SARS wards if the disease comes back.

The authors of the peer-reviewed study, published by BMC Medical Genetics, an online biomedical-research journal, said devising such a genetic-screening system to protect health-care workers from SARS was the main motivation for their research. Such screening systems are almost unheard of in practice. Instituting one would test ethical and legal concepts usually left to the realm of academia.

In May, when the world's first and only known SARS epidemic was still raging, the researchers at Mackay Memorial Hospital came up with the idea for their study. The hospital's transfusion-medicine laboratory, headed by Marie Lin, had spent years amassing data about genes that produce human leukocyte antigens, or HLA, proteins that play an important role in the human immune system.

Combinations of HLA genes vary from person to person. Numerous studies in recent years have linked the variations to differences in the way diseases affect individuals. There is evidence, for example, that some HLA genes provide more protection against leprosy, tuberculosis and the human immune-deficiency virus, while other genes make people more susceptible.

Dr. Lin, a clinical pathologist, said in an interview that she wanted to find out whether a similar dynamic might be at work in SARS patients.

Dr. Lin had been struck by the way SARS seemed to spread mainly among people in southern China, Taiwan, Hong Kong, northern Vietnam and Singapore. From previous research, she was aware of certain HLA genes relatively common to people living in those places -- an apparent vestige of some distant common ancestry -- but rare among other populations around the globe.

She and her colleagues collected blood from 37 local SARS patients and three "control groups" made up of 319 noninfected people. The researchers extracted DNA from the samples and screened it for HLA genes.

What they found surprised them. A gene known as HLA-B46 was discovered in five of the six most severely affected SARS patients in the study. All of those patients required treatment with mechanical ventilators, and all but one died, according to the study. The finding is "statistically significant," Dr. Lin said, because that gene is found only in about 10% to 15% of Taiwan's population. For the gene to be present in nearly all of the study's severely affected SARS patients suggests that more than coincidence might be at play, she said.

The findings also indicate a possible link between the gene and higher rates of susceptibility to SARS. While not all of the SARS patients in the study had the HLA-B46 gene, it was present in 12 of the SARS patients, or nearly twice the rate as in noninfected people.

"The gene seems to be related to infection rates, but we would need a bigger sample" to confirm the findings, she said. "I really hope somebody would do studies in China and Hong Kong to test my hypothesis, to clarify this." The HLA-B46 gene is present at similar rates in southern Chinese, Singaporean, northern Vietnamese and Hong Kong populations, she said, but extremely rare in Africans and Caucasians.

Health authorities say it is much too early to hail the discovery of a "SARS gene." A spokesman for the World Health Organization declined to comment on the study. "We're early in the learning curve about SARS," said the spokesman, Dick Thompson, adding that such studies "may point us in a direction that could be useful, and we need to explore every avenue."

Leondios Kostrikis, a molecular biologist at the University of Cyprus who has published research on the role of patients' genetics in HIV infections, said the Taiwan report appeared to be scientifically sound. "I think the sample size is adequate to pull out this specific hypothesis," Dr. Kostrikis said. "It would be very interesting to see what other studies turn up, in Canada, and so on."

Of course, even if the gene does play a role in the severity of and susceptibility to SARS, the disease clearly is capable of harming people who lack the gene. One of the first people to die of SARS was Italian: Carlo Urbani, a World Health Organization doctor. SARS cases cropped up in 30 countries world-wide. In the SARS outbreak in Toronto, one of the earliest known cases was a woman of Chinese ancestry who was infected during a February trip to Hong Kong's Metropole Hotel. After she returned to Toronto and one of her family members was hospitalized, the disease spread quickly to patients, health-care workers and visitors of many ethnicities.

Some scientists are preparing to follow up. K.Y. Yuen, a SARS expert at the University of Hong Kong, said: "We do not have such data at the moment but will look into it and see what can be done to confirm or refute it."

Write to Matt Pottinger at matt.pottinger@wsj.com

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