18.97.9.175
18.97.9.175
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Non-replication of an obesity GWAS locus rs7138803 (G>A) near FAZM2in a sample of Malaysian subjects
( Yee-how Say ) , ( Ke-en Tan ) , ( Fook-tim Chew )
UCI I410-ECN-0102-2021-500-000673084
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Objective: This study investigated the association of rs7138803 (G)A), an intergenic obesity genetic locus identified through various genome-wide association studies (GWAS), with obesity and its related anthropometric traits among 502 Malaysian subjects (Chinese/Indian: 478/24; M/F: 223/279). The effect of overexpression of the gene nearest to rs7138803, Fas apoptotic inhibitory molecule 2 (FAIM2), on lipid accumuhtion was also investigated in 3T3-L1 differentiated adipocytes. Methods : Blood pressures and anthropometric measurements were taken and genotyping was performed by PCR-RFLP using genomic DNA extracted from mouthwash samples. Lipid accumulation in 3T3-L1 adipocytes transiently transfected with FAIM2 cDNA was assessed by Oil Red O (ORO)assay. Results: The minor allele frequency of rs7138803 in the studied population was 0.30 (Chinese/Indian: 0.30/0.46); genotype distribution was in Hardy- Weinberg equilibrium. Blood pressures and majority of the anthropometric measurements showed no association with rs7138803 genotypes and alleles. Only WHRadjBMI (waist-hip ratio adjusted for BMI) showed significant association with genotype {p = 0.02) and allele = 0.03). Stratified analysis showed that WHR was marginally associated with genotype in males after adjustment for BMI {p = 0.047).ORO assay showed no significant difference in the level of lipid accumulation between controls and adipocytes with FAIM2 overexpression (p = 0.51). Conclusion: rs7138803 was marginally associated with central obesity (WHRadjBMI) in males, but not with blood pressures and other anthropometric measurements indicative of obesity. In vitro transient overexpression of FAIM2 in adipocytes also showed no significant increase in lipid accumulation. Taken together, the role of rs7138803 SNP and FAIM2 in the development of obesity is debatable and further studies are warranted.

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