TY - JOUR
T1 - Age and genetic determinants of variation of circulating levels of the receptor for advanced glycation end products (RAGE) in the general human population
AU - Prakash, Jai
AU - Pichchadze, Guram
AU - Trofimov, Svetlana
AU - Livshits, Gregory
N1 - Publisher Copyright: © 2015 Elsevier Ireland Ltd.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - In stark contrast to many other blood biomarkers, including a variety of inflammatory cytokines, the main factors affecting sRAGE variation in the general human population are virtually unknown. We examined the contribution of age, body composition, and putative genetic sources to the interindividual variation of sRAGE. Its plasma levels were measured in 1557 apparently healthy individuals from 359 nuclear families. Statistical analysis revealed that all the aforementioned factors are statistically significantly associated with sRAGE levels. The levels of sRAGE consistently decreased with age (. R=. -0.264, p=. <0.001) and with the indices of obesity, such as BMI. However, of special interest was the highly significant and previously not reported independent correlation with fat free mass (. p<. 0.001). The putative genetic effects explained 0.291. ±. 0.089 of sRAGE variation and were solely responsible for the phenotypic correlations with the obesity phenotypes (genetic correlations, -0.22. ±. 0.09 and -0.33. ±. 0.09). Taken together, these data suggest that although genetically determined to a substantial degree, the sRAGE levels also depend on age and obesity, which in turn, increase the risk for a variety of pathological conditions associated with sRAGE. Clearly, identifying the metabolic pathways and specific genetic factors is the next important stage in this research area.
AB - In stark contrast to many other blood biomarkers, including a variety of inflammatory cytokines, the main factors affecting sRAGE variation in the general human population are virtually unknown. We examined the contribution of age, body composition, and putative genetic sources to the interindividual variation of sRAGE. Its plasma levels were measured in 1557 apparently healthy individuals from 359 nuclear families. Statistical analysis revealed that all the aforementioned factors are statistically significantly associated with sRAGE levels. The levels of sRAGE consistently decreased with age (. R=. -0.264, p=. <0.001) and with the indices of obesity, such as BMI. However, of special interest was the highly significant and previously not reported independent correlation with fat free mass (. p<. 0.001). The putative genetic effects explained 0.291. ±. 0.089 of sRAGE variation and were solely responsible for the phenotypic correlations with the obesity phenotypes (genetic correlations, -0.22. ±. 0.09 and -0.33. ±. 0.09). Taken together, these data suggest that although genetically determined to a substantial degree, the sRAGE levels also depend on age and obesity, which in turn, increase the risk for a variety of pathological conditions associated with sRAGE. Clearly, identifying the metabolic pathways and specific genetic factors is the next important stage in this research area.
KW - BMI
KW - Fat and fat free mass
KW - Genetic correlations
KW - Heritability
KW - Obesity
KW - RAGE
UR - http://www.scopus.com/inward/record.url?scp=84923038558&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.mad.2015.01.001
DO - https://doi.org/10.1016/j.mad.2015.01.001
M3 - مقالة
C2 - 25681682
SN - 0047-6374
VL - 145
SP - 18
EP - 25
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
ER -