Association Between aquaporin-1 and Endurance Performance: A Systematic Review

Area of Science:

• Genetics and Exercise Physiology
• Molecular Biology
• Human Physiology

Background:

• The Aquaporin-1 (AQP1) gene and channel are crucial for regulating water flow across cell membranes, impacting fluid balance, health, and exercise performance.
• AQP1's role in fluid transport in various cells and its involvement in transporting essential molecules highlight its importance in cardiorespiratory endurance (CE).
• Recent research suggests a link between a specific AQP1 gene variant (rs1049305 C > G) and CE performance, with further associations noted between the AQP1 channel and CE phenotypes.

Purpose of the Study:

• To systematically review and examine the associations between the AQP1 rs1049305 genotype and cardiorespiratory endurance (CE) exercise performance.
• To investigate the relationship between AQP1 rs1049305 genotype and body fluid loss in long-distance runners.
• To explore associations between the AQP1 gene/channel and other CE phenotypes.

Main Methods:

• A comprehensive systematic review of studies published between January 1, 1988, and December 31, 2018, was conducted using major electronic databases (PubMed, EMBASE, CINAHL, Cochrane).
• Eligibility criteria included case-control studies with defined cases/controls, CE defined by endurance events or maximal oxygen consumption, and specific genotyping methods (PCR or sequencing) with reported genotype frequencies.
• Data extraction focused on study details, participant characteristics, CE definitions, genotyping methods, genotype/allele frequencies, and Hardy-Weinberg equilibrium (HWE) for the AQP1 gene variant rs1049305 (C > G) and AQP1 channel function.

Main Results:

• The review synthesized data from 46 studies, confirming an independent association between the AQP1 gene variant rs1049305 (C > G) and CE performance.
• The rs1049305 C-allele was specifically associated with faster CE running performance.
• Aqp1 knockout mice demonstrated reduced running distance, and in vitro studies showed reduced AQP1 expression with the rs1049305 G-allele; however, AQP1 null humans could not support fluid homeostasis under chronic fluid overload, and limited sample sizes precluded in-depth analysis across diverse ethnic groups.

Conclusions:

• The AQP1 gene and channel appear to support homeostatic mechanisms that provide an advantage during endurance exercise.
• AQP1 functions are vital for endurance running performance and cellular homeostasis, both at rest and during exercise.
• The findings support the hypothesis that the AQP1 gene and channel significantly influence cardiorespiratory endurance performance, warranting further research.