(The New York Times News Service) - Researchers have identified the genetic basis of lactose intolerance, the inability of most adults in the world to digest the principal sugar in milk. The finding, published Monday in the journal Nature Genetics, may lead to the development of a more accurate test for the condition.

Lactose intolerance can cause bloating and indigestion from consuming milk or milk products. More than 30 million Americans, mostly black or Asian, are prone to the condition.

Though lactose intolerance may sound like a disorder, it is in fact natural. In most people the gene for lactase, the enzyme that digests lactose, is switched on at birth and switched off at the age of weaning.

In most Europeans, however, the infant condition persists, and the lactase gene remains active. With the domestication of cattle and goats in the Near East some 10,000 years ago, the ability to digest lactose throughout life could have conferred some nutritional advantage. Biologists speculate that a mutation that prolonged the gene's activity was suddenly favored and spread throughout the population.

But one finding has baffled biologists: The gene for the lactase enzyme, as well as the gene's promoter - a neighboring region of DNA that controls the activity of the gene - shows no significant difference between populations whose adults can digest lactose and those whose adults cannot.

Now a team of Finnish and American biologists report that they have identified two single-unit DNA changes that correlate strongly with the presence or absence of adult lactase activity.

The changes were found by studying the sequence of DNA units near the lactase gene in nine Finnish families. About 20 percent of Scandinavians are lactose intolerant, and Finnish scientists had collected elaborate pedigrees of the trait, allowing the precise DNA changes to be identified, said Dr. Leena Peltonen, an author of the study who works at the University of Helsinki.

The DNA changes were not in the lactase gene or its promoter region but in the interior of a neighboring gene that has nothing to do with lactase. Presumably the changes regulate the activity of the lactase gene in some manner yet to be understood.

Dr. Joseph Terwilliger of Columbia University, another author of the study, said so little was known about the control of human genes that he was not surprised to find the lactase gene being regulated from inside an unrelated gene.

Knowledge of the two single-unit DNA changes will allow a genetic test to be designed so that lactose intolerance can be diagnosed from the DNA in a drop of blood, Peltonen said. The condition now is recognized indirectly by such tests as measuring hydrogen in the breath. If lactose is not digested by the lactase enzyme and absorbed, it will be metabolized by bacteria in the gut that generate hydrogen gas.

But some experts do not see any particular need for a genetic test, because they do not regard lactose intolerance as a clinically serious condition. Dr. Michael D. Levitt of the Minneapolis Veterans Affairs Medical Center, whose specialty is the study of intestinal gas, said that in most people an inactive lactase gene was rarely a problem unless they drank large amounts of milk.

Many people who believe they have problems digesting lactose actually have a different condition, irritable bowel syndrome, Levitt said. He reached this conclusion by advertising for patients who believed they had a serious problem with lactose and by feeding them either ordinary milk or milk in which the lactose had been predigested with a lactase pill. There was no difference in their symptoms, he said.

Levitt, who invented the hydrogen test for lactose intolerance, said concern about the condition was "mostly an American phenomenon, and the rest of the world is not much interested in it." He says the concern about lactose has arisen because "there is a tremendous amount of irritable bowel syndrome, and people would like to find a cause for it."

Dr. Stephen James, an official of the National Institute of Diabetes and Digestive and Kidney Diseases, agrees that doctors and patients sometimes get diverted into a hunt for minute traces of lactose in the diet when the real problem is irritable bowel syndrome, a poorly understood condition for which there is no test except ruling out everything else.

People without adult lactase activity would probably notice that they had some gas after drinking two glasses of milk, James said, but he regarded that as "just a variation of normal physiology," not a disease or abnormality.

The authors of the new report say the two single DNA units that switch off the lactase gene are in the ninth and 13th introns in a neighboring gene whose role has to do with the replication of DNA. Introns are the spacer regions of DNA that separate the information-coding parts of a gene. Since the cell cuts out and discards the introns when a gene is activated, these disposable pieces of DNA have long been ignored. Now it seems they play unexpected roles in gene control.

In the default human condition, in which the lactase gene is programmed to turn off after weaning, people have C in the ninth intron position of both their maternal and paternal DNA and G in both the 13th intron positions. But changing the C to a T and the G to an A in either or both sets of a person's DNA keeps the gene from switching off in the cells that line the intestine. (The four letters of the DNA alphabet are A, T, C and G, and one full set of DNA is inherited from each parent.)

Changes in DNA sequence can often be dated. But Terwilliger said there was not enough data from the Finnish families to test the plausible hypothesis that the lactase-enabling mutations had become more common since the domestication of cattle and goats.

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