AVPR2 Gene and Weight Changes During Triathlons

L. de Milander; M. A. Kun; A. V. September; M. P. Schwellnus; T. D. Noakes; M. Collins

doi:10.1055/s-0031-1285865

International Journal of Sports Medicine, Table of Contents

Int J Sports Med 2012; 33(01): 67-75
DOI: 10.1055/s-0031-1285865

Genetics & Molecular Biology

AVPR2 Gene and Weight Changes During Triathlons

L. de Milander

¹Human Biology, University of Cape Town, South Africa

,

M. A. Kun

¹Human Biology, University of Cape Town, South Africa

,

A. V. September

¹Human Biology, University of Cape Town, South Africa

,

M. P. Schwellnus

¹Human Biology, University of Cape Town, South Africa

,

T. D. Noakes

¹Human Biology, University of Cape Town, South Africa

,

M. Collins

²Research Unit for Exercise Science and Sports Medicine, South African Medical Research Council, Cape Town, South Africa

¹Human Biology, University of Cape Town, South Africa

› Author Affiliations

Abstract

The arginine vasopressin receptor 2 (AVPR2) plays an important antidiuretic role in regulating water balance to maintain osmotic equilibrium. The aim of this study was to determine if there were any associations between single nucleotide polymorphisms (SNPs), within the AVPR2 gene, and changes in serum sodium concentrations and/or body weight (BW) in Ironman triathletes. Caucasian male triathletes who completed either the 2000, 2001 or 2006 South African Ironman Triathlons were genotyped (n=570) for at least one SNP. Pre- and post-race serum [Na⁺] (pre n=514; post n=423) and BWs (pre n=556; post n=552) were measured. Triathletes were divided into 3 groups according to their relative BW loss during the triathlon (BW loss of 0–3, 3–5 and >5%). There was a significant linear trend (p=0.010, x²=6.7) for the distribution of minor haplotypes GCT, GTC and GCC across the 3 BW loss groups. The >5% group had the highest percentage (4.7%) of triathletes with minor haplotypes followed by the 3–5% (3.6%) and 3–0% (0%) groups. In conclusion, the minor haplotype constructs of AVPR2 SNPs were associated with larger BW losses during the Ironman Triathlons. This finding supports a possible genetic contribution to BW loss during endurance exercise events acting through the argine vasopression system.

Key words

fluid balance - water homeostasis - electrolyte

Full Text

References

References
1 Almond CS, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, Duncan CN, Olson DP, Salerno AE, Newburger JW, Greenes DS. Hyponatremia among runners in the Boston Marathon. N Engl J Med 2005; 352: 1550-1556
2 Bes DF, Mendilaharzu H, Fenwick RG, Arrizurieta E. Hyponatremia resulting from arginine vasopressin receptor 2 gene mutation. Pediatr Nephrol 2007; 22: 463-466
3 Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008; 40: 695-701
4 Decaux G, Vandergheynst F, Bouko Y, Parma J, Vassart G, Vilain C. Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree. J Am Soc Nephrol 2007; 18: 606-612
5 Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, Lustig RL, Mathias RS, Portale AA, Miller WL, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med 2005; 352: 1884-1890
6 Gupta S, Cheetham TD, Lambert HJ, Roberts C, Bourn D, Coulthard MG, Ball SG. Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis. Eur J Endocrinol 2009; 161: 503-508
7 Harriss DJ, Atkinson G. Update – Ethical Standards in Sport and Exercise Science Research. Int J Sports Med 2011; 32: 819-821
8 Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, Lesch KP. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621-2624
9 Hew-Butler T, Noakes TD, Soldin SJ, Verbalis JG. Acute changes in arginine vasopressin, sweat, urine and serum sodium concentrations in exercising humans: does a coordinated homeostatic relationship exist?. Br J Sports Med 2010; 44: 710-715
10 Hew-Butler T. Arginine vasopressin, fluid balance and exercise: is exercise-associated hyponatraemia a disorder of arginine vasopressin secretion?. Sports Med 2010; 40: 459-479
11 Hew-Butler T, Collins M, Bosch AN, Sharwood K, Wilson G, Armstrong M, Jennings CL, Swart J, Noakes TD. Maintenance of plasma volume and serum sodium concentration despite body weight loss in Ironman triathletes. Clin J Sport Med 2007; 17: 116-122
12 Hew-Butler T, Sharwood K, Boulter J, Collins M, Tucker R, Dugas J, Shave R, George K, Cable T, Verbalis JG, Noakes T. Dysnatremia predicts a delayed recovery in collapsed ultramarathon runners. Clin J Sport Med 2007; 17: 289-296
13 Irving RA, Noakes TD, Buck R, van Zyl Smit R, Raine E, Godlonton J, Norman RJ. Evaluation of renal function and fluid homeostasis during recovery from exercise-induced hyponatremia. J Appl Physiol 1991; 70: 342-348
14 Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration. Front Neuroendocrinol 1997; 18: 292-353
15 Knoers NV. Hyperactive vasopressin receptors and disturbed water homeostasis. N Engl J Med 2005; 352: 1847-1850
16 Lahiri DK, Nurnberger Jr JI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 1991; 19: 5444
17 Lung CC, Chan EK, Zuraw BL. Analysis of an exon 1 polymorphism of the B2 bradykinin receptor gene and its transcript in normal subjects and patients with C1 inhibitor deficiency. J Allergy Clin Immunol 1997; 99: 134-146
18 Noakes TD, Sharwood K, Speedy D, Hew T, Reid S, Dugas J, Almond C, Wharam P, Weschler L. Three independent biological mechanisms cause exercise-associated hyponatremia: evidence from 2,135 weighed competitive athletic performances. Proc Natl Acad Sci USA 2005; 102: 18550-18555
19 Noakes TD. Changes in body mass alone explain almost all of the variance in the serum sodium concentrations during prolonged exercise. Has commercial influence impeded scientific endeavour?. Br J Sports Med 2011; 45: 475-477
20 Pastene J, Germain M, Allevard AM, Gharib C, Lacour JR. Water balance during and after marathon running. Eur J Appl Physiol 1996; 73: 49-55
21 Saunders CJ, de Milander L, Hew-Butler T, Xenophontos SL, Cariolou MA, Anastassiades LC, Noakes TD, Collins M. Dipsogenic genes associated with weight changes during Ironman Triathlons. Hum Mol Genet 2006. 15. 2980-2987
22 Sharwood K, Collins M, Goedecke J, Wilson G, Noakes T. Weight changes, sodium levels, and performance in the South African Ironman Triathlon. Clin J Sport Med 2002; 12: 391-399
23 Sharwood KA, Collins M, Goedecke JH, Wilson G, Noakes TD. Weight changes, medical complications, and performance during an Ironman Triathlon. Br J Sports Med 2004; 38: 718-724
24 Soule S, Florkowski C, Potter H, Pattison D, Swan M, Hunt P, George P. Intermittent severe, symptomatic hyponatraemia due to the nephrogenic syndrome of inappropriate antidiuresis. Ann Clin Biochem 2008; 45: 520-523
25 Spanakis E, Milord E, Gragnoli C. AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol 2008; 217: 605-617
26 Speedy DB, Faris JG, Hamlin M, Gallagher PG, Campbell RG. Hyponatremia and weight changes in an ultradistance triathlon. Clin J Sport Med 1997; 7: 180-184
27 Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence. Biol Psychiatry 2011; in press. 10.1016/j.biopsych.2011.04.017
28 Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 2001; 29: E88