TY - JOUR
T1 - FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population
AU - Hebbar, Prashantha
AU - Abu-Farha, Mohamed
AU - Mohammad, Anwar
AU - Alkayal, Fadi
AU - Melhem, Motasem
AU - Abubaker, Jehad
AU - Al-Mulla, Fahd
AU - Thanaraj, Thangavel Alphonse
N1 - Copyright © 2020 Hebbar, Abu-Farha, Mohammad, Alkayal, Melhem, Abubaker, Al-Mulla and Thanaraj.
PY - 2020/1/31
Y1 - 2020/1/31
N2 - Association studies have implicated single nucleotide polymorphisms (SNPs), particularly rs1421085, from the fat mass and obesity-associated (FTO) gene with body composition phenotypes, obesity, dietary intake, and physical activity in European, East Asian, and African populations. However, the impact of the rs1421085 variant has not been sufficiently tested in ethnic populations (such as Arabs) with high levels of obesity. Further, there is a lack of studies identifying biomarkers that interact with FTO. Therefore, we investigated the association of rs1421085 with obesity and body composition traits and metabolic biomarkers in Arab population. We genotyped rs1421085 SNP in 278 Arab individuals, where multiple biomarkers relating to obesity, inflammation, and other metabolic pathways were quantified. We performed genetic association tests under additive mode of inheritance using linear regression models and found association of rs1421085_C allele with higher levels of body weight, soft lean mass (SLM), and total body water. Examination (using linear regression models under dominant mode of inheritance) of correlation among biomarkers and interaction with genotypes at the variant revealed that measures of these three body composition traits were found mediated by interaction between carrier genotypes (TC+CC) and measures of ghrelin, ApoA1, and ApoB48. Lean body mass (LBM), to which SLM contributes, is an important determinant of physical strength and is a focal point in studies on sarcopenia. Low LBM is known to be associated with higher risk of cardiometabolic disorders. Thus, the finding on the FTO variant as a genetic determinant of SLM via interaction with ghrelin, ApoA1, and ApoB48 is important.
AB - Association studies have implicated single nucleotide polymorphisms (SNPs), particularly rs1421085, from the fat mass and obesity-associated (FTO) gene with body composition phenotypes, obesity, dietary intake, and physical activity in European, East Asian, and African populations. However, the impact of the rs1421085 variant has not been sufficiently tested in ethnic populations (such as Arabs) with high levels of obesity. Further, there is a lack of studies identifying biomarkers that interact with FTO. Therefore, we investigated the association of rs1421085 with obesity and body composition traits and metabolic biomarkers in Arab population. We genotyped rs1421085 SNP in 278 Arab individuals, where multiple biomarkers relating to obesity, inflammation, and other metabolic pathways were quantified. We performed genetic association tests under additive mode of inheritance using linear regression models and found association of rs1421085_C allele with higher levels of body weight, soft lean mass (SLM), and total body water. Examination (using linear regression models under dominant mode of inheritance) of correlation among biomarkers and interaction with genotypes at the variant revealed that measures of these three body composition traits were found mediated by interaction between carrier genotypes (TC+CC) and measures of ghrelin, ApoA1, and ApoB48. Lean body mass (LBM), to which SLM contributes, is an important determinant of physical strength and is a focal point in studies on sarcopenia. Low LBM is known to be associated with higher risk of cardiometabolic disorders. Thus, the finding on the FTO variant as a genetic determinant of SLM via interaction with ghrelin, ApoA1, and ApoB48 is important.
KW - biomarkers
KW - FTO
KW - ghrelin
KW - obesity
KW - soft lean mass
KW - total body water
UR - http://www.scopus.com/inward/record.url?scp=85079615636&partnerID=8YFLogxK
U2 - 10.3389/fgene.2019.01411
DO - 10.3389/fgene.2019.01411
M3 - Article
C2 - 32076432
AN - SCOPUS:85079615636
VL - 10
SP - 1411
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 1411
ER -