Association between peripheral blood growth differentiation factor 15 deoxyribonucleic acid methylation and sarcopenia among the elderly / 中华老年医学杂志

ABSTRACT

Objective:To examine the relationship between sarcopenia and DNA methylation in the promoter of the growth differentiation factor 15(GDF15)gene in elderly individuals.Methods:This cross-sectional study collected data from 865 elderly individuals aged 65 years and above who underwent physical examination at the Yuetang Town Community Medical Center in Yangzhou City between May and September 2020.The verification set included 431 males and 434 females with an age range of 65-100 years and a mean age of(76.0±5.9)years.The diagnosis of sarcopenia was based on the consensus diagnostic criteria of the Asian Sarcopenia Working Group in 2019.The study included 295 cases in the non-sarcopenia group and 470 cases in the sarcopenia group.The study selected 50 non-sarcopenia patients and 50 age-gender matched sarcopenia patients as the explore set for DNA methylation sequencing of the GDF15 gene.The sequencing results were then verified using the methylation-specific polymerase chain(PCR)method in the verification center.Additionally, serum GDF15 levels were detected using the enzyme-linked immunosoradsorption method.The study analyzed the correlation between GDF15 methylation levels, serum GDF15 levels, and sarcopenia.Results:The study found that individuals with sarcopenia had lower levels of body mass index(BMI), appendicular skeletal muscle mass(ASMI), grip strength, and gait speed in both the discovery and validation sets compared to those without sarcopenia( P<0.05). Additionally, the DNA methylation of GDF15 was found to be lower in the sarcopenic group compared to the non-sarcopenic group[93.7%(79.6%, 98.0%) vs.97.7%(95.3%, 99.0%), Z=-9.294, P<0.01]. The results of the correlation analysis indicate a positive relationship between the methylation level and appendicular skeletal muscle mass( r=0.206, P<0.01), grip strength( r=0.297, P<0.01), and gait speed( r=0.383, P<0.01). Conversely, there was a negative correlation between the methylation level and serum GDF15 level( r=-0.249, P<0.05). The study conducted ROC analysis to determine the predictive ability of GDF15 methylation for sarcopenia found that the area under the curve was 0.700 with a cut-off score of 92.7%.Furthermore, binary regression analysis revealed that low GDF15 methylation( OR=1.136, 95% CI: 1.098~1.175, P<0.01)was linked to a higher risk of sarcopenia, even after adjusting for age, sex, and BMI.The serum GDF15 level was higher in the sarcopenic group compared to the non-sarcopenic group[(0.665±0.432)pg/L vs.(0.465±0.211)pg/L( t=-2.452, P<0.05)]. Additionally, it was observed that the methylation of GDF15 was negatively correlated with the serum GDF15 level( r=-0.249, P<0.05). Conclusions:A low level of GDF15 methylation has been found to be linked with a higher risk of sarcopenia, suggesting that measuring GDF15 methylation could potentially serve as a biomarker for diagnosing sarcopenia.