Androgen Receptor CAG Repeat Size is Associated with Stress Fracture Risk: A Pilot Study

Yanovich, Ran; Milgrom, Roni; Friedman, Eitan; Moran, Daniel S.

doi:10.1007/s11999-011-1805-2

Cited by 12 publications

(5 citation statements)

References 36 publications

(49 reference statements)

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“…Associations were shown for SNPs and haplotype blocks within the vitamin D receptor (13) and an androgen receptor repeat sequence (14). However, other studies have shown no association for the same SNPs in similar military populations (15).…”

Section: Introductionmentioning

confidence: 90%

RANK/RANKL/OPG pathway: Genetic associations with stress fracture period prevalence in elite athletes

Varley

Hughes

Greeves³

et al. 2015

Bone

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Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations.Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes.Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays.Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions:The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions.

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Section: Introductionmentioning

confidence: 90%

RANK/RANKL/OPG pathway: Genetic associations with stress fracture period prevalence in elite athletes

Varley

Hughes

Greeves³

et al. 2015

Bone

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“…This could be explained by military personnel having varying roles that encompass a high level of mobility, leaving DNA extraction to become difficult due to absence during deployment, high workload or travel. The predominant method of blood-based extraction is also time consuming in itself and presents difficulty with either reluctance due to needle use31 or obvious problems in self-gathering blood samples. Although little research has been conducted in comparing DNA extraction methods for genetic studies, research has shown that saliva is becoming an accepted and reliable method of DNA extraction, with applications in self-gathered and field-gathered DNA 18 33…”

Section: Discussionmentioning

confidence: 99%

Health and well-being management in the military: a systematic review of genetic studies

2017

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“…Furthermore, larger sized CAG androgen receptor ( AR ) gene repeats (> 16) were more common in Israeli military personnel who had suffered stress fractures (23%) than those who had not suffered this injury (13%) (Yanovich et al 2011). A higher number of CAG repeats within the AR gene are inversely associated with the transcriptional response to testosterone (Zitzmann et al 2001) and deficiency in such hormones could influence bone metabolism and potential bone loss (Mohamad et al 2016; Khosla 2015).…”

Section: Genetic Association With Bmdmentioning

confidence: 99%

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

et al. 2018

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Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.

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Androgen Receptor CAG Repeat Size is Associated with Stress Fracture Risk: A Pilot Study

Abstract: Level II, prognostic study. See the Guidelines for Authors complete description of levels of evidence.

Cited by 12 publications

References 36 publications

RANK/RANKL/OPG pathway: Genetic associations with stress fracture period prevalence in elite athletes

RANK/RANKL/OPG pathway: Genetic associations with stress fracture period prevalence in elite athletes

Health and well-being management in the military: a systematic review of genetic studies

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

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