Daiva Nielsen

Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults

Recent evidence indicates that genetic variation in fatty acid desaturases 1 and 2 (FADS1 and FADS2) is associated with changes in plasma fatty acid profiles; however, the association with altered desaturase activity has not been examined in different ethnic populations. The present study examined whether genetic variation in the FADS gene cluster regulates desaturase activity in two populations of young Canadian adults (Caucasian and Asian) and whether altered desaturase activity was reflected in both n-3 and n-6 fatty acid profiles. FADS1 and FADS2 were genotyped in a random subset of participants (Caucasian, n=78; Asian, n=69) from the Toronto Nutrigenomics and Health study using MALDI-TOF mass spectrometry, and plasma fatty acids were measured by gas chromatography. Desaturase activities were estimated using the following fatty acid ratios: γ-linoleic acid to linoleic acid (GLA:LA), arachidonic acid to linoleic acid (AA:LA), arachidonic acid to dihomo-γ-linoleic acid (AA:DGLA), and eicosapentaneoic acid to α-linolenic acid (EPA:ALA). Nineteen single nucleotide polymorphisms (SNPs) were examined, and several SNPs (9 in Caucasians and 8 in Asians) were associated with various desaturase activities. The most significant association detected was between the FADS1 rs174547 SNP and AA:LA in both Caucasians (p=4.0 × 10(-8)) and Asians (p=5.0 × 10(-5)). Although the minor allele for this SNP differed between Caucasians (T) and Asians (C), carriers of the C allele had a lower desaturase activity than carriers of the T allele in both groups. To determine whether rs174547 was a dominant SNP in the FADS gene cluster, we constructed an additional model which included this SNP as a covariate. Only one SNP (rs498793 in FADS2) remained associated with the EPA:ALA ratio (p=1.1 × 10(-5)) in Asians. This study shows that genetic variation in the FADS gene cluster (in particular rs174547) can alter desaturase activity in subjects of Caucasians and Asian descent.

Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults.

Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease.

Dietary patterns and ethnicity are associated with distinct plasma proteomic groups

BACKGROUND High-abundance plasma proteins are involved in disease-associated pathways and are useful in the diagnosis of nutritional and disease states. However, little is known about how concentrations of many plasma proteins vary between individuals from different ethnocultural groups with different dietary habits. OBJECTIVE We explored the association between plasma proteomic groups, dietary patterns, and ethnicity in the Toronto Nutrigenomics and Health Study, an ethnically diverse population of healthy young adults. DESIGN Concentrations of 54 high-abundance plasma proteins were measured simultaneously by liquid chromatography/multiple-reaction monitoring-mass spectrometry in 1090 individuals. Principal components analysis was used to identify plasma proteomic groups. Linear regression was used to investigate relations between proteomic groups and previously identified dietary patterns (Western, prudent, Eastern). Differences in individual protein concentrations between ethnocultural groups were tested by using general linear models. RESULTS Four independent principal components representative of proteomic groups were identified. Principal components 1 and 2 included proteins from multiple pathways. Component 3 was inflammatory, and component 4 included coagulation cascade proteins. East Asians and South Asians had lower component 1 scores, and East Asians had higher component 2 scores. South Asians had higher average scores for component 3. Individual protein concentrations also varied across ethnocultural groups. Principal component 1 was positively associated with the Western dietary pattern and inversely associated with the Eastern pattern. Component 3 was positively associated with the Eastern pattern. CONCLUSIONS Plasma proteomic groups differ between young adults of diverse ethnocultural groups with different dietary habits. These differences may partly account for different rates of cardiometabolic disease later in life.

Disclosure of genetic information and change in dietary intake: a randomized controlled trial.

Background Proponents of consumer genetic tests claim that the information can positively impact health behaviors and aid in chronic disease prevention. However, the effects of disclosing genetic information on dietary intake behavior are not clear. Methods A double-blinded, parallel group, 2∶1 online randomized controlled trial was conducted to determine the short- and long-term effects of disclosing nutrition-related genetic information for personalized nutrition on dietary intakes of caffeine, vitamin C, added sugars, and sodium. Participants were healthy men and women aged 20–35 years (n = 138). The intervention group (n = 92) received personalized DNA-based dietary advice for 12-months and the control group (n = 46) received general dietary recommendations with no genetic information for 12-months. Food frequency questionnaires were collected at baseline and 3- and 12-months after the intervention to assess dietary intakes. General linear models were used to compare changes in intakes between those receiving general dietary advice and those receiving DNA-based dietary advice. Results Compared to the control group, no significant changes to dietary intakes of the nutrients were observed at 3-months. At 12-months, participants in the intervention group who possessed a risk version of the ACE gene, and were advised to limit their sodium intake, significantly reduced their sodium intake (mg/day) compared to the control group (−287.3±114.1 vs. 129.8±118.2, p = 0.008). Those who had the non-risk version of ACE did not significantly change their sodium intake compared to the control group (12-months: −244.2±150.2, p = 0.11). Among those with the risk version of the ACE gene, the proportion who met the targeted recommendation of 1500 mg/day increased from 19% at baseline to 34% after 12 months (p = 0.06). Conclusions These findings demonstrate that disclosing genetic information for personalized nutrition results in greater changes in intake for some dietary components compared to general population-based dietary advice. Trial Registration ClinicalTrials.gov NCT01353014

Genetic Variation in Putative Salt Taste Receptors and Salt Taste Perception in Humans

The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the SCNN1A (3), SCNN1B (12), SCNN1G (6), and TRPV1 (10) genes affect salt taste perception. Participants were men (n = 28) and women (n = 67) from the Toronto Nutrigenomics and Health study aged 21-31 years. Taste thresholds were determined using a 3-alternative forced-choice staircase model with solutions ranging from 9×10(-6) to 0.5 mol/L. Suprathreshold taste sensitivity to 0.01-1.0 mol/L salt solutions was assessed using general labeled magnitude scales. None of the SNPs in the SCNN1A and SCNN1G genes were significantly associated with either outcome. In the SCNN1B gene, 2 SNPs in intronic regions of the gene modified suprathreshold taste sensitivity (mean iAUC ± SE). Those homozygous for the A allele of the rs239345 (A>T) polymorphism and the T allele of the rs3785368 (C>T) polymorphism perceived salt solutions less intensely than carriers of the T or C alleles, respectively (rs239345: 70.82±12.16 vs. 96.95±3.75, P = 0.02; rs3785368: 57.43±19.85 vs. 95.57±3.66, P = 0.03) In the TRPV1 gene, the rs8065080 (C>T, Val585Ile) polymorphism modified suprathreshold taste sensitivity where carriers of the T allele were significantly more sensitive to salt solutions than the CC genotype (98.3±3.8 vs. 74.1±8.3, P = 0.008). Our findings show that variation in the TRPV1 and the SCNN1B genes may modify salt taste perception in humans.

Enzymatic activity and genetic variation in SCD1 modulate the relationship between fatty acids and inflammation.

Fatty acids (FA) represent a diverse class of molecules known to regulate inflammatory pathways. Therefore enzymes that regulate FA metabolism are attractive candidates to better understand the relationship between FA and inflammation. Stearoyl-CoA desaturase 1 (SCD1) is rate limiting for the conversion of saturated FA (SFA) to monounsaturated FA (MUFA). Evidence suggests that SCD1 activity may be positively associated with inflammation. Moreover, genetic variation in SCD1 may alter enzyme activity; however, it is unknown whether this affects inflammatory status. The goal of this study was to examine the relationships between plasma FA, SCD1 activity, and SCD1 polymorphisms with C-reactive protein (CRP) levels in young adults. SFA, MUFA, and CRP were measured in fasted plasma samples from European (n=279, 198 female and 81 male) and Asian (n=249, 179 female and 70 male) subjects, 20-29 years old. Circulating levels of palmitic (16:0), palmitoleic (16:1), stearic (18:0), and oleic acids (18:1) were measured by gas chromatography and SCD1 activity was estimated by the ratio of product to precursor (16:1/16:0; 18:1/18:0). Positive associations were identified between CRP levels and 16:0 (p<2.0×10(-4)), 16:1 (p<0.05), and the SCD1 index (18:1/18:0; p<6.0×10(-3)) in European and Asian females, while 18:0 was inversely associated with CRP (p<2.0×10(-4)) in both groups. Ten single nucleotide polymorphisms (SNPs) in SCD1 were genotyped in all subjects. One SNP (rs2060792) was associated (p<0.05) with 16:0 and 18:0 levels in females of European descent. This same SNP was also associated with CRP levels in both groups of females (p<0.05). Overall, SCD1 activity and genetic variation have an important role in modulating the relationship between FA and inflammation in young adults.

Variation in the FADS1/2 gene cluster alters plasma n−6 PUFA and is weakly associated with hsCRP levels in healthy young adults

INTRODUCTION Past research has reported that single nucleotide polymorphisms (SNPs) in fatty acid desaturase 1 and 2 (FADS1/2) can influence plasma fatty acid (FA) profiles. Changes in FA profiles are known to influence inflammatory processes; therefore both FA and SNPs in FADS1/2 may affect inflammation. The goals of this study were to (i) examine the relationships between individual n-6 FA and estimates of FA desaturation with circulating high sensitivity C-reactive protein (hsCRP) levels, and (ii) determine whether SNPs in FADS1/2 are associated with changes in hsCRP. METHODS FA and hsCRP were measured in fasted plasma samples from 878 healthy young adults (20-29yrs). Circulating levels of plasma linoleic (LA), γ-linolenic (GLA), dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids were measured by gas chromatography and used to calculate desaturase indices for FADS1/2. Nineteen SNPs in FADS1/2 were genotyped in all subjects and six (rs174579, rs174593, rs174626, rs526126, rs968567 and rs17831757) were further analyzed. RESULTS Significant inverse associations were found between LA and hsCRP (p=8.55×10(-9)) and the FADS1 desaturase index and hsCRP (p=4.41×10(-6)). A significant positive association was found between DGLA and hsCRP (p=9.10×10(-11)). Several SNPs were associated with circulating levels of individual FA and desaturase indices, with minor allele carriers having lower AA levels and reduced desaturase indices. A single SNP in FADS2 (rs526126) was weakly associated with hsCRP (p=0.05). CONCLUSIONS This study highlights the relationships between FA and hsCRP, and confirms that FA are strongly influenced by SNPs in FADS1/2. Furthermore, we found weak evidence that SNPs in FADS1/2 may influence hsCRP levels in young adults.

Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars

Background/Aims: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. Methods: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. Results: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004). Conclusion: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

BACKGROUND Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown. OBJECTIVES This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations. METHODS The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites. RESULTS Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites. CONCLUSION These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.

Ethnicity, sex, FADS genetic variation, and hormonal contraceptive use influence delta-5- and delta-6-desaturase indices and plasma docosahexaenoic acid concentration in young Canadian adults: a cross-sectional study

BackgroundThere is great interest in the relationship between polyunsaturated fatty acids and health. Yet, the combinatory effect of factors such as sex, ethnicity, genetic polymorphisms and hormonal contraceptives (HC) on the concentrations of these fatty acids is unknown. Therefore, we sought to determine the effects of FADS polymorphisms, and HC use in females, on aggregate desaturase indices (ADI), and plasma docosahexaenoic acid (DHA) concentrations in Caucasian and East Asian males and females.MethodsFasting plasma samples were collected from subjects (Caucasian males: 113 and females: 298; East Asian males: 98 and females: 277) from the Toronto Nutrigenomics and Health Study. Fatty acid concentrations were measured by gas chromatography. ADI were estimated by dividing concentrations of arachidonic acid by linoleic acid (n-6 ADI) and eicosapentaenoic acid (EPA) by α-linolenic acid (n-3 ADI). [DHA/EPA] desaturase index was used to determine effects of FADS2 polymorphisms and HC use on EPA conversion to DHA.ResultsIn Caucasians, associations between n-6 ADI and multiple SNP (FADS1 rs174547, FADS2 rs174576, and rs174611 in males; FADS1 rs174547, FADS2 rs174570, rs174576, rs174679, rs174611, rs174593, rs174626, rs2072114, rs2845573, and rs2851682 in females) withstood multiple testing. In East Asian females, 5 SNP-n-6 ADI associations (FADS2 rs174602, rs174626, rs2072114, rs2845573, and rs2851682) withstood multiple testing. One FADS2 SNP was associated with altered [DHA/EPA] desaturase index in Caucasian females only (rs174576, p < 0.0001). HC use had a significant effect on DHA concentrations in Caucasian females only (P < 0.0001).ConclusionsWe demonstrate ethnic- and sex-specific effects of FADS polymorphisms on desaturase indices, and ethnic-specific effect of HC use on plasma DHA concentrations.