Our results have important public health implications given the increasing numbers of people developing diabetes and the need for more powerful interventions, said study author Elina R?¶nnemaa, MD, with Uppsala University in Uppsala, Sweden.

The study involved 2,269 men in Sweden who underwent glucose testing at age 50 to test for diabetes, which is caused by abnormal insulin levels. During an average follow up of 32 years, 102 participants were diagnosed with Alzheimer's disease, 57 with vascular dementia and 235 with other types of dementia or cognitive impairment.

The study found that the men with low insulin secretion capacity at age 50 were nearly one-and-a-half times more likely to develop Alzheimer's disease than people without insulin problems. The risk remained significant regardless of blood pressure, cholesterol, body mass index and education.

Our results suggest a link between insulin problems and the origins of Alzheimer's disease and emphasize the importance of insulin in normal brain function, said R?¶nnemaa. It's possible that insulin problems damage blood vessels in the brain, which leads to memory problems and Alzheimer's disease, but more research is needed to identify the exact mechanisms.

The study also found the association between diabetes and risk of Alzheimer's disease was strongest in people who did not have the APOE4 gene, which is known to increase the risk of Alzheimer's disease. R?¶nnemaa says this shows that insulin problems are an important risk factor for Alzheimer's disease when the high risk gene is missing.

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To see if these results could be generalized from the genetically isolated Hutterite population to a more diverse group, the researchers tested the same variations in the CHI3L1 gene in 178 Caucasian children enrolled in prospective birth cohort, known as COAST, a collaboration led by Robert Lemanske of the University of Wisconsin at Madison.

They also looked for correlations between asthma and SNP -131C/G in two clinical samples, one from the Children's University Hospital in Freiberg, Germany (344 children with asthma and 28, and 94 without), and one from the asthma clinics at the University of Chicago Medical Center (99 children and adults with asthma and 197 without).

In the two clinical samples, those with the CC configuration at position 131 were more likely to have asthma, with CG intermediate and GG the lowest risk of the disease. In the COAST cohort, many subject were still too young to have developed asthma, but the genetic patterns was closely associated with YKL-40 levels, and this association was already present at birth.

The authors suspect that the change from C to G at this site reduces expression of the gene, resulting in lower levels of YKL-40 and protection from asthma.

Although variation in CHI3L1 appears to be one of the most significant genetic triggers yet discovered for susceptibility to asthma, it is far from the sole cause of the disease, the researcher caution. In the Hutterites, it explains 9.4 percent of the variance in YKL-40 levels, suggesting that additional genetic variants also influence these levels. Finding those variations "could identify additional genes," they add, "with significant impact on asthma risk and lung function."

"This evolutionarily ancient pathway involving the innate immune system plays a surprisingly important role in asthma pathogenesis," said Ober, "and a single genetic variant in the CHI3L1 gene may account for most of this risk."

This could have a significant impact on drug development, she added. "For some people, if you block YKL-40 you might dramatically reduce the severity of the disease. Knowing the genotype at SNP -131C might identify those who most likely to benefit from such a treatment."

Asthma is a chronic, treatable disease that causes narrowing of the airways, making breathing difficult at times. More than 22 million people in the United States have asthma, including 6.5 million children under age 18, according to the Centers for Disease Control and Prevention (CDC). The disease generates annual health care costs estimated at $14 billion.

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