Genetics, Vitamin D Supplements Can Predict Patients’ Irisin Hormone Levels

Levels of the hormone irisin in people with Prader-Willi syndrome (PWS) may be related to their genetic background and their intake of vitamin D supplements, a study suggests.

The findings support irisin as a biomarker of cognitive function in adults with the disorder.

The study, “The genetic background and vitamin D supplementation can affect irisin levels in Prader–Willi syndrome,” was published in the Journal of Endocrinological Investigation.

PWS is caused by loss of paternal genes in chromosome 15 that control metabolism, appetite, growth, intellectual skills, and social behavior.

The most common cause is deletion of these genes (called DEL15), while other genetic mechanisms underlying PWS include the inheritance of two copies of chromosome 15 from the mother rather than one from each biological parent — dubbed maternal uniparental disomy (UPD) — and imprinting defects where modifications are made to DNA in sperm and egg cells.

As for bone health, adolescents and adults with PWS experience lower bone mineral density and bone mineral content, raising the risk of osteoporosis (weak and brittle bones) and other complications.

Irisin is a hormone secreted by muscles in response to exercise and is known to affect metabolic parameters in muscle and fat cells. Its levels have been associated with an increase in bone mass, and recent data have reported the hormone’s effect on certain brain functions and role in cognitive impairment.

However, the role of irisin in PWS has not been fully explored. As such, a team from Italy sought to understand the link between blood levels of irisin in PWS patients and their genetic background, metabolic profile, cognitive function, and bone health.

The study included 26 children (mean age 9.48 years) and 52 adults (mean age 30.6 years) with PWS. To serve as age-matched controls, the study also included 26 children who visited the hospital for minor surgery or electrocardiographic screening of heart function, and 54 adults with normal weight.

Genetic background from all patients was studied: DEL15 was found in 32 adults and 16 children, whereas UPD was detected in 20 adults and 10 children.

Children had been treated with growth hormone (GH) for at least one year, with a daily dose ranging from 0.025 to 0.035 mg/kg. Six adult patients received GH at a mean dose of 0.23 mg/day.

Vitamin D supplements were taken by four children (15%) and by half the adults with PWS. Daily doses were 12.5 micrograms in children and 20 micrograms in adults.

Height, weight, body mass index (a measure of body fat), fat mass, fat free mass, bone mineral density, and bone mineral content were also determined.

Blood levels of irisin, glucose, insulin, total cholesterol, HDL and LDL cholesterol (known as “good” and “bad” cholesterol), and triglycerides (a type of fat) were among the parameters measured.

The intelligence quotient (IQ) was used to assess cognitive function with specific scales for children and adults.

Results showed that blood concentration of irisin was not significantly different between patients and controls. However, the hormone levels were lower in children and adults with DEL15 than in controls.

In children with PWS, the only two parameters that differed between the DEL15 and UPD groups were total cholesterol and LDL, as they were lower in those with genetic deletion.

Adult patients on vitamin D supplementation had similar irisin levels relative to controls, but they had higher levels than patients not taking such supplements.

The findings also showed that low levels of irisin were related to no vitamin D supplementation in adults with DEL15 or UPD.

These results may indicate that “vitamin D supplementation has an important role in regulating irisin levels in adult PWS patients,” the researchers wrote.

Both genetics and vitamin D levels predicted irisin levels in patients with PWS, the researchers concluded. Particularly in children, hormone levels were mostly predicted by weight, genetic background, blood levels of vitamin D, and bone mineral density.

In adult patients, genetics, IQ, vitamin D levels, bone mineral density, sex steroid replacement therapy as well as growth hormone treatment (and its duration and age at the start of treatment) were the best predictors of irisin levels. The link with growth hormone and sex steroid replacement therapy suggests “the key role of the beginning of the therapy to normalize the levels of [irisin] in these subjects,” the researchers wrote.

Also, the association with IQ supports the role of irisin as a biomarker of cognitive impairment in adults with PWS.