Ruth Birk

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Genes and elite athletes: a roadmap for future research

Abstract  There is compelling evidence that genetic factors influence several phenotype traits related to physical performance and training response as well as to elite athletic status. Previous case‐control studies showed that ∼20 genetic variants seem to be associated with elite endurance athletic status. The present review aims to introduce novel methodological approaches in the field of sports genetics research, which can be applied in the near future to analyse the genotype profile associated with elite athletic status. These include genotype–phenotype association studies using gene expression analysis, analysis of post‐transcriptional factors, particularly microRNAs, genome‐wide scan linkage or genome‐wide association studies, and novel algorithm approaches, such as ‘genotype scores’. Several gaps in the current body of knowledge have been indentified including, among others: small sample size of most athletic cohorts, lack of corroboration with replication cohorts of different ethnic backgrounds (particularly, made up of non‐Caucasian athletes), the need of research accounting for the potential role of epigenetics in elite athletic performance, and also the need for future models that take into account the association between athletic status and complex gene–gene and gene–environment interactions. Some recommendations are provided to minimize research limitations in the field of sport genetics.

The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes

The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34–0.48; P = 0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07–3.31; P = 0.028). In endurance athletes, the OR of a “world-class” competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08–12.94; P = 0.038) compared with those of a lower (“national”) competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance.

Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1

Autosomal recessive lethal congenital contractural syndrome (LCCS) is a severe form of neuromuscular arthrogryposis. We previously showed that this phenotype is caused in two unrelated inbred Bedouin tribes by different defects in the phosphatidylinositol pathway. However, the molecular basis of the same phenotype in other tribes remained elusive. Whole exome sequencing identified a novel LCCS founder mutation within a minimal shared homozygosity locus of approximately 1 Mb in two affected individuals of different tribes: a homozygous premature stop producing mutation in MYBPC1, encoding myosin‐binding protein C, slow type. A dominant missense mutation in MYBPC1 was previously shown to cause mild distal arthrogryposis. We now show that a recessive mutation abrogating all functional domains in the same gene leads to LCCS. Hum Mutat 33:1435–1438, 2012.

The FTO A/T Polymorphism and Elite Athletic Performance: A Study Involving Three Groups of European Athletes

Objective The FTO A/T polymorphism (rs9939609) is a strong candidate to influence obesity-related traits. Elite athletes from many different sporting disciplines are characterized by low body fat. Therefore, the aim of this study was to assess whether athletic status is associated with the FTO A/T polymorphism. Subjects and Methods A large cohort of European Caucasians from Poland, Russia and Spain were tested to examine the association between FTO A/T polymorphism (rs9939609) and athletic status. A total of 551 athletes were divided by type of sport (endurance athletes, n = 266 vs. sprint/power athletes, n = 285) as well as by level of competition (elite-level vs. national-level). The control group consisted of 1,416 ethnically-matched, non-athletic participants, all Europeans. Multinomial logistic regression analyses were conducted to assess the association between FTO A/T genotypes and athletic status/competition level. Results There were no significantly greater/lesser odds of harbouring any type of genotype when comparing across athletic status (endurance athletes, sprint/power athletes or control participants). These effects were observed after controlling for sex and nationality. Furthermore, no significantly greater/lesser odds ratios were observed for any of the genotypes in respect to the level of competition (elite-level vs. national-level). Conclusion The FTO A/T polymorphism is not associated with elite athletic status in the largest group of elite athletes studied to date. Large collaborations and data sharing between researchers, as presented here, are strongly recommended to enhance the research in the field of exercise genomics.

Detoxification of cassava by Aspergillus niger B-1

Abstract The effects of fermentation of cassava by Aspergillus niger B-1 β-glucosidase on its cyanide and protein content, and the optimal conditions for this enzyme’s activity, were examined. This fermentation process reduced the cyanide content of cassava by 95% to 2 mg/kg, and increased its total protein content by 50%, thereby improving its nutritional value. A significant decrease in cyanogenic glycosides was detected after 3 days of fermentation. The optimal pH for A. nigerβ-glucosidase activity on the cyanogenic glycoside linamarin was determined to be 3, the optimal temperature 55 °C, and its Km 0.3 mM. The findings presented here will facilitate the development of an improved method for detoxification of cassava and for enhancement of its nutritional value.

BBS4 directly affects proliferation and differentiation of adipocytes

BBS4 is one of several proteins whose defects cause Bardet–Biedl syndrome (BBS), a multi-systemic disorder, manifesting with marked obesity. BBS4 polymorphisms have been associated with common non-syndromic morbid obesity. BBS4 obesity molecular mechanisms, and the role of the BBS4 gene in adipocyte differentiation and function are not entirely known. We now show that Bbs4 plays a direct and essential role in proliferation and adipogenesis: silencing of Bbs4 in 3T3F442A preadipocytes induced accelerated cell division and aberrant differentiation, evident through morphologic studies (light, scanning and transmission electron microscopy), metabolic analyses (fat accumulation, fatty acid profile and lipolysis) and adipogenic markers transcripts (Cebpα, Pparγ, aP2, ADRP, Perilipin). Throughout adipogenesis and when challenged with fat load, Bbs4 silenced cells accumulate significantly more triglycerides than control adipocytes, albeit in smaller (yet greater in number) droplets containing modified fatty acid profiles. Thus, greater fat accumulation in the silenced cells is a consequence of both a higher rate of adipocyte proliferation and of aberrant differentiation leading to augmented aberrant accumulation of fat per cell. Our findings suggest that the BBS obesity might be partly due to a direct role of BBS4 in physiological and pathophysiological mechanisms that underlie adipose tissue formation relevant to obesity.

Regulation of Pancreatic Lipase by Dietary Medium Chain Triglycerides in the Weanling Rat

Pancreatic lipase (PL) and its related protein 1 (PLRP1) are regulated by the amount of dietary fat through an apparent transcriptional mechanism. Regulation of PL and PLRP1 by type of fat (chain length and degree of saturation) is less well understood. The aim of this study was to determine whether medium-chain triglycerides regulate PL and PLRP1. For 7 d, weanling (21-d-old) Sprague Dawley male rats were fed diets low (11% of energy), moderate (40% of energy), or high (67% of energy) in trioctanoate/tridecanoate (MCT) or safflower (low fat only) oils. Food consumption decreased as dietary MCT increased, and the consumption of MCT diets was lower than that of the low-safflower (control) diet. Final body weight was similar among rats fed the low- or moderate-MCT or control diets, but was significantly reduced (17%) in those fed the high-MCT diets. PL activity was significantly elevated 53–60% (p < 0.002) in rats fed low and moderate MCT diets, respectively, compared with that of rats fed high-MCT or control diets. PL and PLRP1 mRNA levels were not significantly different among diets, suggesting that chain length regulates PL and PLRP1 translationally or posttranslationally. The β-hydroxybutyrate plasma concentration was significantly (p < 0.02) higher (85%) in rats consuming low-MCT diet compared with those of rats fed the control diet. MCT at low levels, but not high levels, increase PL activity without changing its mRNA levels.

Synthesis of lsopropyl-1-thio-Β-D-glucopyranoside (IPTGlc), an inducer ofaspergillus niger b1 Β-glucosidase production

Production of Β-glucosidase inAspergillus niger Bl is subjected to catabolic repression by glucose.Aspergillus niger Bl grown on bran as a carbon source secreted Β-glucosidase. The maximum level of the enzyme was reached after 7 d of fermentation. Addition of 1% glucose to the medium suppressed Β-glucosidase production to undetectable levels. In this study, the organic synthesis of a potential inducer of Β-glucosidase production by A.niger Bl’s reported. Isopropyl-1-thio-Β-D-glucopyranoside (IPTGlc) was synthesized using a two-step organic synthesis protocol. The H-NMR data agreed with those reported previously for the galactoside analog. When IPTGlc was added 24 h after inoculation at a final concentration of 0.4 mM, similar levels of Β-glucosidase were reached 3 to 4 d earlier as compared to fermentation without IPTGlc induction. In practice, this may translate to a more efficient method of producing Β-glucosidase from this fungus.

The rs12594956 polymorphism in the NRF-2 gene is associated with top-level Spanish athlete's performance status

OBJECTIVES To determine the association between the nuclear respiratory factor 2 (NRF-2) polymorphisms and elite athletic performance. DESIGN We compared the genotype and allele frequencies of the NRF-2 A/C (rs12594956), NRF-2 A/G (rs7181866), and NRF-2 C/T (rs8031031) polymorphisms between world-class endurance athletes (n=89), elite power-oriented athletes (n=38), and non-athletic controls (n=110) of the same Caucasian (Spanish) origin. METHODS Genomic DNA was extracted from peripheral EDTA-treated, anti-coagulated blood using a standard protocol. Genotyping was performed using polymerase chain reaction (PCR). RESULTS The frequency of the AA genotype of the NRF-2 A/C (rs12594956) polymorphism was significantly higher in endurance athletes compared with power athletes (P<0.01) and controls (P<0.01) (48% vs. 13% and 21%, respectively). The likelihood of having the AA (rs12594956) genotype was higher in elite endurance athletes compared with controls [odds ratio (OR): 3.536, 95% confidence interval (CI): 1.903-6.571] and elite power athletes (OR: 6.170, 95%CI: 2.206-17.253). CONCLUSIONS Our results suggest that the NRF-2 A/C polymorphism might belong to a growing group of polymorphisms associated with endurance performance at the elite level. However, it is important to replicate these findings in other groups of elite athletes using larger sample sizes.