Seasonal gene expression affects drug effectiveness and metabolism in primates, study shows microbiologystudy

Nagoya University researchers in Japan have found that drug effectiveness, alcohol tolerance, and carbohydrate metabolism change with the seasons. Their findings are based on a comprehensive seasonal gene expression map, which investigated over 54,000 genes in 80 tissues in monkeys across one year. The study has implications for drug prescription and precision medicine.

To cope with dynamic seasonal changes in the environment, animals, including humans, have evolved a biological clock that is calibrated to the seasons. Physiology and behavior, including hormone secretion, metabolism, sleep, immune function, and reproduction, change depending on the season.

To understand the nature of these changes, a research group led by Professor Takashi Yoshimura of Nagoya University’s Institute of Transformative Bio-Molecules (ITbM) turned to rhesus monkeys, a primate closely related to humans. Their analysis, reported in Nature Communications, identified multiple “seasonally variable genes” from a comprehensive gene expression map of more than 54,000 genes expressed in 80 tissues.

The study identified seasonal fluctuations in genes responsible for drug metabolism, particularly CYP2D6 and CYP2C19, which affect a quarter of common medications. Several widely used pharmaceuticals may be affected by these seasonal variations, including treatments for cancer, diabetes, high cholesterol, psychiatric conditions, hormonal therapies, and immunosuppressants used in organ transplantation.

Alcohol tolerance depends on season

To test for changes in alcohol tolerance, the team reared mice under winter and summer conditions. They found that mice reared under winter conditions recovered from alcohol intoxication more quickly.

“This result suggests that the body is more likely to become intoxicated in the summer,” Yoshimura said. “This was an interesting discovery as this may explain why the number of patients hospitalized for acute alcohol intoxication is higher in the summer in most countries.”

Women and men may differ in diet

The group found an unexpected sex difference in seasonal variation genes. Although the monkeys were fed the same diet throughout the year, the activity of genes involved in the metabolism of carbohydrates peaked during winter and spring in the duodenum of the female monkeys.

Increased carbohydrate metabolism in the duodenum is important for the body to extract the maximum amount of energy from scarce food in the winter months, which may explain why people often gain weight during this period. Then, as food becomes more available in spring, carbohydrate metabolism is enhanced to extract energy from a more diverse diet.

Chronotherapy may revolutionize our responses to these conditions

Understanding how our genes affect our response to pharmaceuticals, weight gain and alcohol intoxication may help patients.

“Our findings suggest that we should consider the time of year when administering certain medications,” Yoshimura said. “We expect that our research will contribute to chronotherapy and the future of precision medicine.”