Can IGF-I polymorphism affect power and endurance athletic performance?

Abstract

Objective

Insulin-like growth factor-I (IGF-I) plays a key role in exercise-associated muscle growth and development. The regulatory region of the promoter of the IGF-I gene is labile, but changes in this region were studied mostly in the elderly and in relation to pathological states. C-1245T (rs35767) is a genetic variation in the promoter region of the IGF-I gene. The minor allele T was found to be associated with higher circulating IGF-I levels, and possibly with increased muscle mass. The aim of the current study was to analyze the frequency distribution of C-1245T SNP in athletic and nonathletic Israeli populations.

Design

One hundred and sixty-five athletes (78 endurance-type athletes, and 87 power-type athletes) and 159 nonathletic healthy individuals participated in the current study. Genomic DNA was extracted from peripheral EDTA treated anti-coagulated blood using a standard protocol. Genotyping of the IGF1 C-1245T polymorphism was performed using polymerase chain reaction (PCR).

Results

We found that the endurance and power athletes' allele and genotype frequencies were significantly different from those of the control group. Only 4.8% of the athletes were TT carriers, but none of the controls carried this genotype. The T allele was found to be more frequent in the top-level power athletes (international and Olympic level) compared to national level athletes, but such a difference was not found in endurance athletes.

Conclusion

Our findings suggest a possible contribution for the relatively rare IGF-I TT genotype to endurance performance, and in particular to power sport excellence in Israeli athletes.

Introduction

In recent years studies have demonstrated that changes in insulin-like growth factor-I (IGF-I) play a key role in exercise-associated muscle growth and development [1], [2], [3], [4], [5], [6], [7]. Previous studies described that both functional (i.e. maximal oxygen consumption—VO₂max) and structural (i.e. thigh muscle volume determined by magnetic resonance images) indices of fitness were correlated with serum IGF-I levels in pre and late pubertal girls [8], [9]. Although casual connections cannot be concluded, these cross-sectional data suggest that fitness in healthy, non-professional, pre-pubertal and adolescent females may be associated with anabolic adaptations of the GH-IGF-I system. Other studies in professional adolescent rhythmic gymnasts demonstrated no difference in circulating IGF-I levels compared to sedentary controls despite reduced adiposity and leptin levels [10]. However, since IGF-I is affected by energy balance, reduced body weight and fat mass is often associated with decreased IGF-I levels. Therefore, the authors suggested that exercise training preserved IGF-I levels in the rhythmic gymnasts. It should be noted that in young females estrogen levels may also influence IGF-I level and IGF-I local skeletal muscle local sensitivity [11]. Similar correlations between fitness and IGF were found among adults as well [12]. Moreover, changes in IGF-I level may be of importance for the skeletal muscle training adaptation, not only for anabolic myofibrillar structure effects, but also for tendons, ligaments, connective tissue and/or bone adaptations [13], [14], [15].

The human gene encoding IGF-I is located on chromosome 12 [16]. The regulatory region of the PI promoter of IGF-I gene is labile [17]. These changes were analyzed in relation to various pathological states [17], [18], [19], [20], [21], [22], [23] but rarely studied in athletes.

C-1245T (rs35767) is a genetic variation in the promoter region of the IGF-I gene, with the T allele being the minor allele. The C-1245T SNP was found to be associated with circulating IGF-I levels, with the minor T allele related to higher circulating IGF-I levels [24], [25], [26]. Along with its relation to elevated resting serum IGF-I, this 192-bp polymorphism (HapMap, http://www.hapmap.org) [27] was found also to be associated with left ventricular hypertrophy (LVH) [20], [28], enhanced response to eccentric arm exercise [29], greater muscle strength response to resistance training [30] and higher bone density [31]. In contrast, the C allele was associated with increased fasting insulin and insulin resistance [32], and the CC genotype was found to be associated with phenotypes that may represent reduced IGF-I function in elderly, mainly African-American, women [33].

Since it is well recognized that the IGF-I gene plays a role in muscle growth and development, it is possible that the IGF-I C-1245T SNP, known to affect serum IGF-I concentration, is one of the polymorphisms that may be related to elite athletic performance. Therefore, the purpose of this study was to analyze the frequency distribution of C-1245T SNP (rs35767) in athletic and nonathletic Israeli populations, and to compare the frequency distribution of the above polymorphism between athletes of sports with different demands (endurance vs. power) as well as between competitive standards (elite vs. national level). We hypothesized that since increased circulating IGF-I may be possibly associated with increased muscle mass, and since muscle mass is more important to power sports, the relatively rare T/T polymorphism will be significantly higher among power athletes.