Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese

Glutathione S-transferases (GSTs) are the major detoxifying Phase II enzyme for eliminating electrophilic compounds. Mutations in GSTM1, GSTP1 and GSTT1 in Caucasian and GSTA1 in Chinese have been found to reduce enzyme activity. However, data on the impact of common genetic polymorphisms of GSTM1 and GSTP1 on enzyme activity in Chinese is lacking. This study aimed to investigate the effect of common GSTP1 and GSTM1 polymorphisms on erythrocyte GST activity in healthy Chinese (n = 196). GSTM1 null mutation (GSTM1*0) was analyzed by a PCR-Multiplex procedure, whereas GSTP1 313A → G polymorphism (resulting in Ile105Val at codon 105) was analyzed by PCR-restriction fragment length polymorphism (RFLP) analysis. Erythrocyte GST activity was measured using 1-chloro-2,4-dinitro-bezene (CDNB) as the model substrate. The frequency of GSTM1 null genotype was 54.3% and the frequency of GSTP1-Ile/Ile, -Ile/Val, and -Val/Val genotype was 60.7%, 35.2% and 4.1%, respectively, with a frequency of 21.7% for the 105 valine allele. Age, gender and smoking did not significantly affect the erythrocyte GST activities. The mean erythrocyte GST enzyme activity for GSTP1*-Ile/Val genotype group (3.53 ± 0.63 U/g Hb) was significantly lower than that for subjects with GSTP1-Ile/Ile genotype (4.25 ± 1.07 U/g Hb, P = 0.004), while subjects with the GSTP1-Val/Val genotype had the lowest enzyme activity (2.44 ± 0.67 U/g Hb). In addition, the GST activity in carriers of GSTM1*0/GSTP1-Ile/Ile was significantly higher than that of subjects inherited GSTM1*0/GSTP1-Ile/Val or GSTM1*0/GSTP1-Val/Val. However, there is no association between GSTM1 null mutation and reduced enzyme activity. GSTP1 codon 105 mutation led to reduced erythrocyte GST activity in Chinese. A combined GSTP1 and GSTM1 null mutations also resulted in significantly reduced GST activity. Further studies are needed to explore the clinical implications of GSTM1 and GSTP1 polymorphisms.

Differential response to resistance training in CHF according to ACE genotype

Background : The Angiotensin Converting Enzyme (ACE) gene may influence the risk of heart disease and the response to various forms of exercise training may be at least partly dependent on the ACE genotype. We aimed to determine the effect of ACE genotype on the response to moderate intensity circuit resistance training in chronic heart failure (CHF) patients.

Methods : The relationship between ACE genotype and the response to 11 weeks of resistance exercise training was determined in 37 CHF patients (New York Heart Association Functional Class = 2.3 ± 0.5; left ventricular ejection fraction 28 ± 7%; age 64 ± 12 years; 32:5 male:female) who were randomised to either resistance exercise (n = 19) or inactive control group (n = 18). Outcome measures included VO_2peak power output and muscle strength and endurance. ACE genotype was determined using standard methods.

Results : At baseline, patients who were homozygous for the I allele had higher VO_2peak (p = 0.02) and peak power (p = 0.003) compared to patients who were homozygous for the D allele. Patients with the D allele, who were randomised to resistance training, compared to non-exercising controls, had greater peak power increases (ID p < 0.001; DD p < 0.001) when compared with patients homozygous for the I allele, who did not improve. No significant genotype-dependent changes were observed in VO_2peak, muscle strength, muscle endurance or lactate threshold.

Conclusion : ACE genotype may have a role in exercise tolerance in CHF and could also influence the effectiveness of resistance training in this condition.

Maternal 25-hydroxyvitamin D concentration and offspring birth size : effect modification by infant VDR genotype

Background/Objectives: We tested the hypothesis that the relationship between maternal 25-hydroxyvitamin D (25-(OH)D) and offspring birth size differs according to offspring vitamin D receptor (VDR) genotype (Apa1, Bsm1, Fok1 or Taq1).

Subjects/Methods: Mothers of 354 singleton babies had serum 25-(OH)D concentration measured at 28–30 weeks of gestation and consented to measurement of their babies soon after birth. DNA was extracted from the babies’ Guthrie cards.

Results: There was evidence of effect modification by infant FokI genotype. Babies of deficient mothers had lower birth weight with FF or Ff, but not ff genotype (P-value for interaction after adjustment for potential confounding factors=0.02), but thicker subscapular and suprailiac skinfolds with ff, but not FF or Ff genotype (P=0.008 and 0.02, respectively). Sample size was insufficient to investigate effect modification by the other VDR polymorphisms.

Conclusions: These preliminary findings suggest that studies of maternal vitamin D status and birth size may need to take VDR genotype into account.

Introgression of domesticated alleles into a wild trout genotype and the impact on seasonal survival in natural lakes

We tested the fitness consequences of introgression of fast-growing domesticated fish into a wild population. Fry from wild and domesticated rainbow trout (Oncorhynchus mykiss) crosses, F1 hybrids, and first- and second-generation backcrosses were released into two natural lakes. Parentage analysis using microsatellite loci facilitated the identification of survivors, so fitness was estimated in nature from the first-feeding stage. Results indicated that under certain conditions, domesticated fish survived at least as well as wild fish within the same environment. Relative growth and survival of the crosses, however, were highly dependent on environment. During the first summer, fastest-growing crosses had the highest survival, but this trend was reversed after one winter and another summer. Although the F1 hybrids showed evidence of outbreeding depression because of the disruption of local adaptation, there was little evidence of outbreeding depression in the backcrosses, and the second-generation backcrosses exhibited a wild-type phenotype. This information is relevant for assessing the multigenerational risk of escaped or released domesticated fish should they successfully interbreed with wild populations and provides information on how to minimize detrimental impacts of a conservation breeding and/or management programme. These data also further understanding of the selection pressures in nature that maintain submaximal rates of growth.

Hemoglobin genotype has minimal influence on the physiological response of juvenile atlantic cod (Gadus morhua) to environmental challenges

Hemoglobin (Hb) polymorphism in cod is associated with temperature‐related differences in biogeographical distribution, and several authors have suggested that functional characteristics of the various hemoglobin isoforms (HbIs) directly influence phenotypic traits such as growth rate. However, no study has directly examined whether Hb genotype translates into physiological differences at the whole animal level. Thus, we generated a family of juvenile Atlantic cod consisting of all three main Hb genotypes (HbI‐1/1, HbI‐2/2, and HbI‐1/2) by crossing a single pair of heterozygous parents, and we compared their metabolic and cortisol responses to an acute thermal challenge (10°C to their critical thermal maximum [CTM] or 22°C, respectively) and tolerance of graded hypoxia. There were no differences in routine metabolism (at 10°C), maximum metabolic rate, metabolic scope, CTM (overall mean 22.9° ± 0.2°C), or resting and poststress plasma cortisol levels among Hb genotypes. Further, although the HbI‐1/1 fish grew more (by 15%–30% during the first 9 mo) when reared at 10° ± 1°C and had a slightly enhanced hypoxia tolerance at 10°C (e.g., the critical O2 levels for HbI‐1/1, HbI‐2/2, and HbI‐1/2 cod were 35.56% ± 1.24%, and 40.20% ± 1.99% air saturation, respectively), these results are contradictory to expectations based on HbI functional properties. Thus, our findings (1) do not support previous assumptions that growth rate differences among cod Hb genotypes result from a more efficient use of the oxygen supply—that is, reduced standard metabolic rates and/or increased metabolic capacity—and (2) suggest that in juvenile cod, there is no selective advantage to having a particular Hb genotype with regards to the capacity to withstand ecologically relevant environmental challenges.

Association between serotonin transporter genotype, brain structure and adolescent onset major depressive disorder: a longitudinal prospective study

The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13–19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.

Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome, but not overweight or obesity

Background The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence. Aims and methods This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale. Results PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder. Discussion PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.

Effect of genotype and sex on fiber growth rate of alpacas for their first year of fleece production

The sale of alpaca fiber is the main income for thousands of families in the Central Andes of Peru. Little information exists on the fiber length growth rate of alpaca (FLG), especially throughout their first year of life when the fiber is most valuable. We aimed to determine the monthly FLG of 22 alpaca offspring of two genotypes (9 Suri, 13 Huacaya) and considering sex differences (10 females, 12 males) in the High Andes of Peru. FLG growth was determined using dye-bands. An additive lineal model with three factors (genotype, sex, month) was used for statistic analysis. To evaluate the effect of genotype and sex on the profile of the FLG throughout the year a two factor repeated-measures model was used. The results showed that FLG was affected by genotype and month but not sex. The Suri genotype had 20% higher FLG than Huacaya genotype alpacas (1.34 vs 1.10 cm/month, P < 0.001). FLG increased over each of the first three months (P < 0.05) and then maintained a near constant rate for the remainder of the first year. The resulting staple length indicates that shearing at ages from 8 to 12 months of age will provide fleeces of sufficient length for textile processing.

Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: the Food4Me study

OBJECTIVE: To examine whether the effect of FTO loci on obesity-related traits could be modified by physical activity (PA) levels in European adults. METHODS: Of 1,607 Food4Me participants randomized, 1,280 were genotyped for FTO (rs9939609) and had available PA data. PA was measured objectively using accelerometers (TracmorD, Philips), whereas anthropometric measures [BMI and waist circumference (WC)] were self-reported via the Internet. RESULTS: FTO genotype was associated with a higher body weight [β: 1.09 kg per risk allele, (95% CI: 0.14-2.04), P = 0.024], BMI [β: 0.54 kg m(-2) , (0.23-0.83), P < 0.0001], and WC [β: 1.07 cm, (0.24-1.90), P = 0.011]. Moderate-equivalent PA attenuated the effect of FTO on BMI (P[interaction]  = 0.020). Among inactive individuals, FTO increased BMI by 1.06 kg m(-2) per allele (P = 0.024), whereas the increase in BMI was substantially attenuated among active individuals (0.16 kg m(-2) , P = 0.388). We observed similar effects for WC (P[interaction]  = 0.005): the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals. CONCLUSIONS: PA attenuates the effect of FTO genotype on BMI and WC. This may have important public health implications because genetic susceptibility to obesity in the presence of FTO variants may be reduced by adopting a physically active lifestyle.

Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study

The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AA v. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (Ptrend=0·028) and 3·1 cm greater WC (Ptrend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.

Associations between FTO genotype and total energy and macronutrient intake in adults: a systematic review and meta-analysis

Risk variants of fat mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrient intake has not been reviewed systematically. Our aim was to evaluate the potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in OVID MEDLINE, Scopus, EMBASE and Cochrane of associations between macronutrient intake and FTO genotype in adults. Beta coefficients and confidence intervals (CIs) were used for per allele comparisons. Random-effect models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213,173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal day(-1) (95% CI: 10.76, 2.16) lower total energy intake (P = 0.003). Total fat (P = 0.028) and protein (P = 0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P = 0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrient intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.