Fe-deficiency anaemia is a major public health concern in children under 5 years of age. TMPRSS6 gene, encoding matriptase-2 protein, is implicated in Fe homoeostasis and has been associated with anaemia and Fe status in various populations. The aim of this cross-sectional study was to investigate the associations between the single nucleotide polymorphism (SNP) TMPRSS6 rs855791 and biomarkers of anaemia and Fe deficiency in Brazilian children attending day care centres. A total of 163 children aged 6–42 months were evaluated. Socio-economic, demographic, biochemical, haematological, immunological and genotype data were collected. Multiple logistic and linear regressions with hierarchical selection were used to assess the effects of independent variables on categorised outcomes and blood marker concentrations. Minor allele (T) frequency of rs855791 was 0·399. Each copy of the T allele was associated with a 4·49-fold increased risk of developing anaemia (P = 0·005) and a 4·23-fold increased risk of Fe deficiency assessed by serum soluble transferrin receptor (sTfR) (P < 0·001). The dose of the T allele was associated with an increase of 0·18 mg/l in sTfR concentrations and reductions of 1·41 fl and 0·52 pg in mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), respectively. In conclusion, the T allele of SNP TMPRSS6 rs855791 was significantly associated with anaemia and Fe deficiency assessed by sTfR in Brazilian children attending day care centres. The effect was dose dependent, with each copy of the T allele being associated with lower MCV and MCH and higher concentrations of sTfR.

Mitochondria play a key role in cell homeostasis as a major source of intracellular energy (adenosine triphosphate), and as metabolic hubs regulating many canonical cell processes. Mitochondrial dysfunction has been widely documented in many common diseases, and genetic studies point towards a causal role in the pathogenesis of specific late-onset disorder. Together this makes targeting mitochondrial genes an attractive strategy for precision medicine. However, the genetics of mitochondrial biogenesis is complex, with over 1,100 candidate genes found in two different genomes: the nuclear DNA and mitochondrial DNA (mtDNA). Here, we review the current evidence associating mitochondrial genetic variants with distinct clinical phenotypes, with some having clear therapeutic implications. The strongest evidence has emerged through the investigation of rare inherited mitochondrial disorders, but genome-wide association studies also implicate mtDNA variants in the risk of developing common diseases, opening to door for the incorporation of mitochondrial genetic variant analysis in population disease risk stratification.

Tamoxifen is commonly prescribed for preventing recurrence in patients with breast cancer. However, the responses of the patients on tamoxifen treatment are variable. Cytochrome P450 genetic variants have been reported to have a significant impact on the clinical outcomes of tamoxifen treatment but no tangible conclusion can be made up till now. The present review attempts to provide a comprehensive review on the associative relationship between genetic polymorphisms in cytochrome P450 enzymes and survival in breast cancer patients on adjuvant tamoxifen therapy. The literature search was conducted using five databases, resulting in the inclusion of 58 studies in the review. An appraisal of the reporting quality of the included studies was conducted using the assessment tool from the Effective Public Health Practice Project (EPHPP). Meta-analyses were performed on CYP2D6 studies using Review Manager 5.3 software. For other studies, descriptive analyses were performed. The results of meta-analyses demonstrated that shorter overall survival, disease-free survival and relapse-free survival were found in the patients with decreased metabolisers when compared to normal metabolisers. The findings also showed that varying and conflicting results were reported by the included studies. The possible explanations for the variable results are discussed in this review.

Evidence shows that genetic polymorphisms in perilipin 1 gene (PLIN1) are associated with excessive accumulation of body fat and disturbances in cardiometabolic markers. Therefore, the aim of this study was to verify whether the SNP PLIN1 11482 G>A (rs894160) interacts with nutrient intake, anthropometric, body composition and cardiometabolic markers in adults with normal-weight obesity (NWO) syndrome. A cross-sectional study was carried out with 116 individuals aged 20–59 years, with normal BMI and high percentage of body fat. Anthropometric and body composition measures, glycaemic control and serum lipid markers, SNP PLIN1 11482 G>A and nutrient intake were evaluated. Interactions between nutrient intake and the SNP were determined by regression models and adjusted for potential confounders. The SNP frequency was 56·0 % GG, 38·8 % GA and 5·2 % AA. Anthropometric measures and biochemical markers were not different according to genotype, except for total cholesterol (TC), LDL-cholesterol and non-HDL-cholesterol concentrations. However, important interactions between the SNP and dietary intake were observed. Carbohydrate intake interacted with the SNP PLIN1 11482 G>A to modulate waist circumference (WC) and the homeostatic model assessment of insulin resistance index. Interaction of lipid intake and the SNP modulated TC and LDL-cholesterol concentrations, and the interaction between protein intake and the SNP tended to modulate weight, WC and BMI. The SNP PLIN1 11482 G>A seems to modulate responses in anthropometric and lipid profile biomarkers of subjects with NWO depending on the dietary macronutrient composition, which may have long-term impact on cardiometabolic markers.

Identification of a new axis of angiotensin-converting enzyme 2 (ACE2)/angiotensin (1–7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE2 catabolizes angiotensin II and produces angiotensin (1–7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin 1–7 receptor) exhibit anxiety-like behaviours. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to selective serotonin reuptake inhibitors (SSRIs). In a randomised control trial, 200 newly diagnosed Iranian patients with major depressive disorder completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction method. Our results show that the A allele and AA and GA genotypes were significantly associated with better response to SSRIs (p = 0.008; OR = 3.4; 95% CI = 1.4–8.5 and p = 0.027; OR = 3.3, 95% CI = 1.2–9.2, respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (p = 0.0002; OR = 9.1; 95% CI = 2.4–33.7). The A allele was significantly associated with better response to sertraline (p = 0.0001; OR = 7.6; 95% CI = 2.5–23.3). In conclusion, our results confirm the role of G8790A in response to some SSRIs.

Recent evidence has raised the possibility of the existence of a sixth taste modality – that is, taste for fat – which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.

The neurotransmitter serotonin has a role in affective disorders such as depression and anxiety, as well as sleep, cognitive function and appetite. This review examines the evidence that serotonin-related genotypes may moderate the behavioural effects of supplementation with the serotonin precursor amino acid l-tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT) depends. However, 95 % of serotonin is synthesised and used in the periphery, and TRP is also metabolised via non-5-HT routes such as the kynurenine pathway. Moreover, understanding of genotypes involved in regulation of serotonin raises questions over the generalisability of TRP effects on behaviour across individuals with varied serotonergic genotypes. To date, only differences between variants of the 5-HT transporter-linked promoter region (5-HTTLPR) have been investigated in relation to behavioural effects of TRP supplementation. Effects of 5-HTTLPR genotypes are usually compared between the alleles that are either high (L/L′) or low (S/S′) expressing of mRNA for the 5-HT transporter receptor. Yet, another key genetic variable is sex: in women, the S/S′ genotype predicts sensitivity to improved mood and reduced cortisol by TRP supplementation, during stressful challenges, whereas the L/L′ genotype protects against stress-induced mood deterioration. In men, the L/L′ genotype may confer risk of stress-induced increases in negative affect; there are insufficient data to assess effects on male S/S′ genotypes. However, better-powered studies to detect sex by genotype by stress by TRP interactions, as well as consideration of more genotypes, are needed before strong conclusions and recommendations for behavioural effects of TRP treatment can be reached.

Herbicides targeting grass plastidic acetyl coenzyme A carboxylase (ACC) are effective selective graminicides. Their intensive use worldwide has selected for resistance genes in a number of grass weed species. Biochemistry and molecular biology have been the means of determining the herbicidal activity and selectivity toward crop plants of ACC-inhibiting herbicides. In recent years, elucidation of the tridimensional structure of ACC and identification of five amino acid residues within the ACC carboxyl transferase domain that are critical determinants for herbicide sensitivity shed light on the basis of ACC-based resistance to herbicides. However, metabolism-based resistance to ACC-inhibiting herbicides is much less well known, although this type of resistance seems to be widespread. A number of genes thus endow resistance to ACC-inhibiting herbicides, with the possibility for various resistance genes that confer dominant resistance at the herbicide field rate to accumulate within a single weed population or plant. This, together with a poor knowledge of the genetic parameters driving resistance, renders the evolution of resistance to ACC-inhibiting herbicides unpredictable. Future research should consider developing tactics to slow the spread of resistance. For this purpose, it is crucial that our understanding of metabolism-based resistance improves rapidly because this mechanism is complex and can confer resistance to herbicides with different target sites.

The cytochrome P450 iso-enzyme system plays a key role in the biotransformation of many drugs, including psychotropics. Its activity is determined by both genetic and environmental factors. The most important iso-enzymes for psychiatry in general are P450 IID6, 3A4 and 1A2. Knowledge about the involvement of these enzymes and biotransformation processes is mandatory because of the individual variability in their metabolic capacity. Regular measurement of plasmaconcentrations of (psycho)pharmacological compounds is therefore essential. In addition, the potential value of pheno- and/or genotyping has to be investigated.

Genetic association studies of the cytokine interleukin-10 (IL-10) and sepsis have provided inconsistent results. This work attempts to further quantitatively assess the association of three widely evaluated polymorphisms of IL-10 (−592C/A, −819C/T, −1082A/G) with sepsis susceptibility through a meta-analysis. A search of Pubmed, Web of Science and EMBASE databases was performed. Overall, the three polymorphisms have no strong association with sepsis risk. Subgroup analysis by ethnicity showed there was association between sepsis susceptibility with −592C/A in Caucasians (A vs. C: OR 0·78, 95% CI 0·62–1·00, P = 0·05; AA + CA vs. CC: OR 0·75, 95% CI 0·56–1·00, P = 0·05), and with −1082A/G in Asians (G vs. A: OR 1·41, 95% CI 1·04–1·91, P = 0·03; GG + AG vs. AA: OR 2·11, 95% CI 1·07–4·16, P = 0·03). This meta-analysis suggests that −592C/A and −1082A/G polymorphisms are associated with sepsis susceptibility in Caucasian, and Asian populations, respectively.

Several studies have evaluated the association between mannose-binding lectin (MBL) polymorphisms and sepsis. However, the results are inconclusive and conflicting. To better understand the roles of MBL polymorphisms in sepsis, we conducted a comprehensive meta-analysis. All relevant studies were searched from PubMed, EMBASE and Web of Knowledge databases, with the last report up to 7 May 2013. Twenty-nine studies addressing four MBL polymorphisms (–550G/C, –221G/C, structure variant A/O, Gly54Asp) were analysed for susceptibility to sepsis and one study for sepsis-related mortality. Overall, significant associations between structure variant A/O and susceptibility to sepsis were observed for AO + OO vs. AA [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·05–1·52, P = 0·01] and O vs. A (OR 1·19, 95% CI 1·02–1·40, P = 0·03). In subgroup analysis based on age group, increased risk was found in the paediatric group in the dominant model (OR 1·72, 95% CI 1·16–2·56, P = 0·007). Moreover, there was a slight association between the +54A/B polymorphism and susceptibility to sepsis in Caucasians (recessive model: OR 10·64, 95% CI 1·24–91·65, P = 0·03). However, no association was observed for –550G/C and –221G/C polymorphisms both overall and in subgroup analysis. For sepsis-related mortality, only one study suggested AO/OO was associated with in-hospital mortality in pneumococcal sepsis patients after controlling for confounding variables. Our meta-analysis indicated that MBL structure variants might be associated with susceptibility to sepsis but further studies with a large sample size should be conducted to confirm these findings.

Genetic disturbances in folate metabolism may increase risk for congenital heart defects. We examined the association of heart defects with four polymorphisms in folate-related genes (methylenetetrahydrofolate reductase (MTHFR) c.677C > T, MTHFR c.1298A > C, methionine synthase reductase (MTRR) c.66A > G, and reduced folate carrier (SLC19A1) c.80A > G) in a case–control study of children (156 patients, 69 controls) and mothers of children with heart defects (181 patients, 65 controls), born before folic acid fortification. MTRR c.66A > G in children modified odds ratios for overall heart defects, specifically ventricular septal defect and aortic valve stenosis (p-value below 0.05). The 66GG and AG genotypes were associated with decreased odds ratios for heart defects (0.42, 95% confidence interval (0.18–0.97) and 0.39 (0.18–0.84), respectively). This overall association was driven by decreased risk for ventricular septal defect for 66GG and AG (odds ratio 0.32 (0.11–0.91) and 0.25 (0.09–0.65)) and decreased odds ratio for aortic valve stenosis for 66AG (0.27 (0.09–0.79)). The association of ventricular septal defect and 66AG remained significant after correction for multiple testing (p = 0.0044, multiple testing threshold p = 0.0125). Maternal MTHFR 1298AC genotype was associated with increased odds ratio for aortic valve stenosis (2.90 (1.22–6.86), p = 0.0157), but this association did not meet the higher multiple testing threshold. No association between MTHFR c.677C > T or SLC19A1 c.80A > G and heart defect risk was found. The influence of folate-related polymorphisms may be specific to certain types of heart defects; larger cohorts of mothers and children with distinct sub-classes are required to adequately address risk.

Hulled wheats are neglected crops that have potential in plant breeding programmes of modern durum and common wheat. Among these wheats, three species were widely cultivated in Spain until the mid 20th century: Triticum monococcum ssp. monococcum (einkorn), Triticum turgidum ssp. dicoccum (emmer) and Triticum aestivum ssp. spelta (spelt). One important aspect of wheat grain quality is starch composition, which is related to the action of waxy proteins. A collection of 536 accessions of Spanish hulled wheats was analyzed for waxy protein composition using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Polymorphism was found for the Wx-A1, Wx-B1 and Wx-D1 proteins, including new and null alleles in the three species. An allelic variant with an electrophoretic mobility not previously described was found in einkorn wheat. In emmer and spelt, some alleles with different mobility were also found. A Wx-B1 null allele was detected in emmer wheat, and null alleles for Wx-A1, Wx-B1 and Wx-D1 were found in spelt wheat. The variations found could be used to enlarge the gene pool available to breeders, and to design new cultivars with different levels of amylose content.

Twenty-nine Leishmania infantum strains characterized by different host source, tropism and belonging to 6 zymodemes, were examined by restriction enzyme analysis of kinetoplast DNA (kDNA) using 15 endonucleases. The enzymes which produced only one fragment revealed full identity between all the strains examined, while those producing many bands gave different electrophoretic patterns. They were interpreted with the aid of numerical analyses (cluster and multifactorial analysis). The results show a cline of genetic variability among the strains, the highest similarity being observed between most of the viscerotropic strains isolated from man, dog, black rat and sandflies. The strain agents of human cutaneous leishmaniasis show a varying degree of genetic divergence from this group, which appears more evident when characters from isoenzymes are considered.

Goat’s αS1-casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell–cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function.

Despite a great deal of research effort there is still considerable uncertainty surrounding the importance of the B-vitamins in health and disease. This continuing uncertainty is partly a result of the difficulty of measuring intake, confounding in observational studies and the very large numbers required to evaluate primary prevention in randomised controlled trials. Consequently, genetic data are increasingly being used to infer nutritional effects on health and even in the formulation of nutrition policy using the approach of ‘mendelian randomisation’. Genetic information has already contributed greatly to the understanding of B-vitamin metabolism and the heterogeneity of responses to intake. It has the potential to provide further nutritional insights and to assist in the elucidation of causal mechanisms, but it is important that genetic data is not viewed as an alternative to nutritional information, both are necessary when addressing nutritional problems. Similarly, the interpretation of nutrient and biomarker status in some experimental designs may require knowledge of genotype. Formal tests of gene–gene and gene–nutrient interaction are of limited value in nutritional studies and the formulation of policy. Graphical representation of diet–genotype–health data greatly assists in the elucidation of the nature of genetic effects, their interaction with nutrition and the implications for nutrition policy.