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Alloveda Liver Update: Association between Single Nucleotide Polymorphisms in PPARA and EPAS1 Genes and High-Altitude Appetite Loss

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eMediNexus    26 May 2020

Loss of appetite is a common symptom encountered at high altitudes (HA) for lowlanders. Hypoxia has been reported to be the key initiating factor of HA appetite loss. Evidence also points to key roles of PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 in hypoxic responses.

A study by Pan et al investigated the link of these hypoxia-related gene polymorphisms with HA appetite loss. Investigators recruited 416 young men who had rapidly ascended to a high altitude (3700 m) from an altitude of <500m by plane. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 were genotyped. Appetite scores were assessed to identify HA appetite loss. Logistic regression and multiple genetic models helped evaluate the association between the single nucleotide polymorphisms (SNPs) and risk of HA appetite loss in crude and adjusted (age and SaO2) analysis. The linkage disequilibrium (LD), haplotype construction and the association of diverse haplotypes with the risk of HA appetite loss were assessed.

Allele “A” in PPARA rs4253747 was found to be significantly associated with the increased risk of HA appetite loss. Codominant, dominant, recessive, and log-additive models of PPARA rs4253747 demonstrated heightened risk of HA appetite loss in the crude and adjusted analysis. On the other hand, only dominant, overdominant, and log-additive models of EPAS1 rs6756667 exhibited a decreased risk of HA appetite loss in the crude and adjusted analysis. Haplotype-based test demonstrated a link between rs7292407-rs6520015 haplotype “AC” and HA appetite loss in the crude analysis.

The study thus demonstrated an association of SNPs in PPARA (rs4253747) and EPAS1 (rs6756667) genes with susceptibility to HA appetite loss in young men.

Source: Pan W, Liu C, Zhang J, et al. Association Between Single Nucleotide Polymorphisms in PPARA and EPAS1 Genes and High-Altitude Appetite Loss in Chinese Young Men. Front Physiol. February 4, 2019.

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