36 research outputs found
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The influence of one-carbon metabolism gene polymorphisms and gene-environment interactions on homocysteine, vitamin B12, folate and lipids in a Brazilian adolescent population
Background: Several single-nucleotide polymorphisms (SNPs) have been associated with the metabolism of Vitamin B12, folic acid, homocysteine and lipids. However, the interaction between SNPs involved in the one-carbon metabolism pathway and macronutrient intake on cardiovascular risk factors in the Brazilian population has not yet been investigated. Hence, the present study examined whether the association of ten SNPs involved in the one-carbon metabolism pathway with Vitamin B12, folic acid, homocysteine and lipid levels is modified by dietary factors and physical activity in adolescents with cardiovascular risk. Materials and Methods: A total of 113 adolescents (10–19 years old), from a public school in the city of Goiânia, Goiás, Brazil, underwent anthropometric, biochemical and food consumption evaluations and genetic tests. Results: After adjusting for potential confounders, SNPs rs4633 (catechol-O-methyltransferase, COMT), rs602662 (fucosyltransferase 2, FUT2) and rs1801394 (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) showed significant associations with folic acid (P = 0.042), Vitamin B12 (P = 0.009) and oxidised low-density lipoprotein (ox-LDL) (P = 0.041) concentrations, respectively. The COMT SNP rs4680 showed a significant interaction with carbohydrate intake on ox-LDL concentrations (Pinteraction = 0.005). In addition, the FUT2 SNP rs602662 showed a significant interaction with protein intake on homocysteine concentrations (Pinteraction = 0.007). However, after correction for multiple testing, none of these associations and interactions were statistically significant. Conclusions: For the first time, we provide evidence for the interactions between COMT SNP rs4680 and carbohydrate intake on ox-LDL levels and the FUT2 SNP rs602662 and protein intake on homocysteine concentrations. However, replication of our results in a larger sample size is required to confirm our findings
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Vitamin D supplementation and immune-related markers: an update from nutrigenetic and nutrigenomic studies
Vitamin D is both a nutrient and a neurologic hormone that plays a critical role in modulating immune responses. While low levels of vitamin D are associated with increased susceptibility to infections and immune-related disorders, vitamin D supplementation has demonstrated immunomodulatory effects that can be protective against various diseases and infections. Vitamin D receptor is expressed in immune cells that have the ability to synthesise the active vitamin D metabolite. Thus, vitamin D acts in an autocrine manner in a local immunologic milieu in fighting against infections. Nutrigenetics and nutrigenomics are the new disciplines of nutritional science that explore the interaction between nutrients and genes using distinct approaches to decipher the mechanisms by which nutrients can influence disease development. Though molecular and observational studies have proved the immunomodulatory effects of vitamin D, only very few studies have documented the molecular insights of vitamin D supplementation. Until recently, researchers have investigated only a few selected genes involved in the vitamin D metabolic pathway that may influence the response to vitamin D supplementation and possibly disease risk. This review summarises the impact of vitamin D supplementation on immune markers from nutrigenetics and nutrigenomics perspective based on evidence collected through a structured search using PubMed, EMBASE, Science Direct and Web of Science. The research gaps and shortcomings from the existing data and future research direction of vitamin D supplementation on various immune-related disorders are discussed
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Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals
Background: High milk intake has been associated with cardio-metabolic risk. We conducted a Mendelian Randomization (MR) study to obtain evidence for the causal relationship between milk consumption and cardio-metabolic traits using the lactase persistence (LCT-13910 C>T, rs4988235) variant as an instrumental variable.
Methods: We tested the association of LCT genotype with milk consumption (for validation) and with cardio-metabolic traits (for a possible causal association) in a meta-analysis of the data from three large-scale population-based studies (1958 British Birth Cohort, Health and Retirement study, and UK Biobank) with up to 417,236 participants and using summary statistics from consortia meta-analyses on intermediate traits (N=123,665 to 697,307) and extended to cover disease endpoints (N=86,995 to 149,821).
Results: In the UK Biobank, carriers of ‘T’ allele of LCT variant were more likely to consume milk (P=7.02x10-14). In meta-analysis including UK Biobank, the 1958BC, the HRS, and consortia-based studies, under an additive model, ‘T’ allele was associated with higher body mass index (BMI) (Pmeta-analysis=4.68x10-12) and lower total cholesterol (TC) (P=2.40x10-36), low-density lipoprotein cholesterol (LDL-C) (P=2.08x10-26) and high-density lipoprotein cholesterol (HDL-C) (P=9.40x10-13). In consortia meta-analyses, ‘T’ allele was associated with a lower risk of coronary artery disease (OR:0.86, 95% CI:0.75-0.99) but not with type 2 diabetes (OR:1.06, 95% CI:0.97-1.16). Furthermore, the two-sample MR analysis showed a causal association between genetically instrumented milk intake and higher BMI (P=3.60x10-5) and body fat (total body fat, leg fat, arm fat and trunk fat; P<1.37x10-6) and lower LDL-C (P=3.60x10-6), TC (P=1.90x10-6) and HDL-C (P=3.00x10-5).
Conclusions: Our large-scale MR study provides genetic evidence for the association of milk consumption with higher BMI but lower serum cholesterol levels. These data suggest no need to limit milk intakes with respect to cardiovascular disease risk, with the suggested benefits requiring confirmation in further studies
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A genetic approach to study the relationship between maternal Vitamin D status and newborn anthropometry measurements: the Vitamin D pregnant mother (VDPM) cohort study
Purpose
Adverse effects of maternal vitamin D deficiency have been linked to adverse pregnancy outcomes. We investigated the relationship between maternal vitamin D status and newborn anthropometry measurements using a genetic approach and examined the interaction between genetic variations in involved in vitamin D synthesis and metabolism and maternal vitamin D concentrations on newborn anthropometry.
Methods
The study was conducted in 183 pregnant Indonesian Minangkabau women. Genetic risk scores (GRSs) were created using six vitamin D–related single nucleotide polymorphisms and their association with 25-hydroxyvitamin D [25(OH)D] levels and newborn anthropometry (183 infants) were investigated.
Results
There was no significant association between maternal 25(OH)D concentrations and newborn anthropometry measurements (P > 0.05, for all comparisons). After correction for multiple testing using Bonferroni correction, GRS was significantly associated with 25(OH)D in the third trimester (P = 0.004). There was no association between GRS and newborn anthropometric measurements; however, there was an interaction between GRS and 25(OH)D on head circumference (P = 0.030), where mothers of neonates with head circumference < 35 cm had significantly lower 25(OH)D if they carried ≥4 risk alleles compared to those who carried ≤3 risk alleles.
Conclusion
Our findings demonstrate the impact of vitamin D-related GRS on 25(OH)D and provides evidence for the effect of vitamin D-related GRS on newborn anthropometry through the influence of serum 25(OH)D levels among Indonesian pregnant women. Even though our study is a prospective cohort, before the implementation of vitamin D supplementation programs in Indonesia to prevent adverse pregnancy outcomes, further large studies are required to confirm our findings
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The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults
BACKGROUND:
Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults.
FINDINGS:
Healthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively.
CONCLUSIONS:
In summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake
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A nutrigenetic approach for investigating the relationship between vitamin B12 status and metabolic traits in Indonesian women
Purpose: Adverse effects of maternal vitamin B12 deficiency have been linked to major clinical outcomes, including increased body mass index and gestational diabetes, however, less is known about vitamin B12 nutrition in non-pregnant women. Hence, the aim of the present study was to explore the relationships between metabolic traits and vitamin B12 status in a cohort of healthy Indonesian women and to investigate whether these relationships were modified by dietary intake using a genetic approach.
Methods: A total of 117 Minangkabau women (aged 25-60 years), from the city of Padang, West Sumatra underwent anthropometric, biochemical, dietary intake analysis and genetic tests. Genetic risk scores (GRS) based on nine vitamin B12 associated single nucleotide polymorphisms (SNPs) (B12-GRS) and nine metabolic SNPs (metabolic-GRS) were constructed.
Results: The B12-GRS and metabolic-GRS had no effect on vitamin B12 (P>0.160) and metabolic traits (P>0.085). However, an interaction was observed between the B12-GRS and dietary fibre intake (g) on glycated haemoglobin (HbA1C) levels (P interaction=0.042), where among those who consumed a low fibre diet (4.90 ± 1.00 g/day), individuals carrying ≥9 risk alleles for vitamin B12 deficiency had significantly higher HbA1C levels (P=0.025) compared to those carrying ≤8 risk alleles.
Conclusion: Our study showed a significant impact of the B12-GRS on HbA1C concentrations through the influence of a dietary factor, however, our study failed to provide evidence for an impact of metabolic-GRS on lowering B12 concentrations. Further replication studies utilizing larger sample sizes are needed to confirm our findings
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Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians
Background: Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach and investigate whether these associations are modified by lifestyle factors.
Methods: The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing.
Results: The ‘A’ allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p=1.90 x 10-47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p=7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of ‘A’ allele with cardiometabolic health status disappeared (p=0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons).
Conclusions: Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases
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Association between pre-pregnancy body mass index and gestational weight gain on pregnancy outcomes: a cohort study in Indonesian pregnant women
Background: Pre-pregnancy BMI (PP BMI) and gestational weight gain (GWG) are prominent anthropometric indicators for maternal nutritional status and are related to an increased risk of adverse pregnancy outcomes. This study
aimed to determine the factors afecting total GWG, PP BMI and pregnancy outcomes among pregnant women in
West Sumatra, Indonesia.
Methods: This observational analysis was conducted among healthy women in the Vitamin D Pregnant Mother
(VDPM) cohort study. A total of 195 pregnant women and their newborn babies were enrolled, and information
regarding their socio-demographic characteristics, obstetric history, dietary intake and anthropometric data were
assessed through direct interviews. Furthermore, the Institute of Medicine (IOM) 2009 guidelines were used to obtain
the total GWG.
Results: PP BMI was used to categorise the 195 pregnant women as overweight/obese (43.1%), normal (46.7%) and
underweight (10.2%). There were 53.3%, 34.4% and 12.3% of women who had inadequate, adequate and excessive
GWG, respectively. The multinomial logistic regression model indicated that overweight or obese women at the
pre-pregnancy stage were 4.09 times more likely to have an excessive rate of GWG (AOR=4.09, 95% CI: 1.38–12.12,
p=0.011) than those whose weight was normal. Furthermore, women with excessive GWG were 27.11 times more
likely to have a baby with macrosomia (AOR=27.11, 95% CI: 2.99–245.14) (p=0.001) and those with inadequate
GWG were 9.6 times more likely to give birth to a baby with low birth weight (LBW) (AOR=9.60, 95% CI; 0.88–105.2)
(p=0.002).
Conclusions: This study demonstrates that the malnutrition status prior to pregnancy and inadequate or excessive
GWG status during pregnancy as signifcant risk factors for developing adverse pregnancy outcomes. These fndings
highlight the importance of providing information, preconception counselling and health education on weight management for healthy pregnancies
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Impact of maternal dietary carbohydrate intake and vitamin D-related genetic risk score on birth length: the Vitamin D Pregnant Mother (VDPM) cohort study
Background: Our objectives were to investigate the relationship between maternal vitamin D status and IGF-1 levels in healthy Minangkabau pregnant mothers and their impact on newborn anthropometry outcomes and to examine whether this relationship was modified by dietary intake using a nutrigenetic approach.
Methods: Healthy singleton pregnant mother and infant pairs (n=183) were recruited. We created three genetic risk scores (GRSs): a six-SNP GRS based on six vitamin D-related single nucleotide polymorphisms (SNPs) involved in the synthesis of vitamin D (vitamin D-GRS), a two-SNP GRS using SNPs in VDR genes (VDR-GRS) and a four-SNP GRS using SNPs from DHCR7, GC, CYP24A1 and CYP2R1 genes (non-VDR GRS). The effect of the GRSs on IGF-1, vitamin D and newborn anthropometry and the interaction between the GRSs and dietary factors were tested using linear regression analysis.
Results: The vitamin D- and non-VDR GRSs were significantly associated with lower 25(OH)D concentration (p=0.005 and p=0.001, respectively); however, there was no significant association with IGF-1, and newborn anthropometry outcomes. However, there was a significant interaction of VDR-GRS with carbohydrate intake on birth length outcome (Pinteraction=0.032). Pregnant mothers who had higher carbohydrate intake (405.88 ± 57.16 g/day) and who carried ≥2 risk alleles of VDR-GRS gave birth to babies with significantly lower birth lengths compared to babies born to mothers with <2 risk alleles (p=0.008).
Conclusion: This study identified a novel interaction between VDR-GRS and carbohydrate intake on birth length outcome. These findings suggest that reducing the intake of carbohydrates during pregnancy, particularly for those who have a higher genetic susceptibility, might be an effective approach for preventing foetal growth abnormalities