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Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study.

https://arctichealth.org/en/permalink/ahliterature290863
Source
BMJ Open. 2017 06 10; 7(6):e016154
Publication Type
Journal Article
Date
06-10-2017
Author
Cecilia Lourdudoss
Alicja Wolk
Lena Nise
Lars Alfredsson
Ronald van Vollenhoven
Author Affiliation
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Source
BMJ Open. 2017 06 10; 7(6):e016154
Date
06-10-2017
Language
English
Publication Type
Journal Article
Keywords
Adult
Aged
Antirheumatic Agents - therapeutic use
Arthritis, Rheumatoid - drug therapy
Dietary Supplements
Fatty Acids, Omega-3 - administration & dosage
Female
Folic Acid - administration & dosage
Humans
Male
Middle Aged
Prospective Studies
Sweden
Vitamin D - administration & dosage
Vitamins - therapeutic use
Abstract
Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA).
This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3?months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders.
The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline.
Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs.
Notes
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PubMed ID
28601838 View in PubMed
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The association between marine n-3 polyunsaturated fatty acid levels and survival after renal transplantation.

https://arctichealth.org/en/permalink/ahliterature271524
Source
Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1246-56
Publication Type
Article
Date
Jul-7-2015
Author
Ivar A Eide
Trond Jenssen
Anders Hartmann
Lien M Diep
Dag O Dahle
Anna V Reisæter
Kristian S Bjerve
Jeppe H Christensen
Erik B Schmidt
My Svensson
Source
Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1246-56
Date
Jul-7-2015
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Cause of Death
Chromatography, Gas
Cohort Studies
Fatty Acids, Omega-3 - administration & dosage - blood
Female
Fishes
Humans
Kaplan-Meier Estimate
Kidney Transplantation - adverse effects - mortality
Linear Models
Male
Middle Aged
Multivariate Analysis
Norway
Proportional Hazards Models
Protective factors
Registries
Risk factors
Seafood
Time Factors
Treatment Outcome
Young Adult
Abstract
Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants.
In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation.
There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (=7.95 weight percentage) compared with low levels (
Notes
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PubMed ID
26063768 View in PubMed
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Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism.

https://arctichealth.org/en/permalink/ahliterature80057
Source
Int J Cancer. 2007 Jan 15;120(2):398-405
Publication Type
Article
Date
Jan-15-2007
Author
Hedelin Maria
Chang Ellen T
Wiklund Fredrik
Bellocco Rino
Klint Asa
Adolfsson Jan
Shahedi Katarina
Xu Jianfeng
Adami Hans-Olov
Grönberg Henrik
Bälter Katarina Augustsson
Author Affiliation
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. maria.hedelin@ki.se
Source
Int J Cancer. 2007 Jan 15;120(2):398-405
Date
Jan-15-2007
Language
English
Publication Type
Article
Keywords
Aged
Animals
Cyclooxygenase 2 - genetics
Diet
Fatty Acids, Omega-3 - administration & dosage
Fish Oils - administration & dosage
Fish Products
Humans
Male
Membrane Proteins - genetics
Polymorphism, Single Nucleotide
Prostatic Neoplasms - epidemiology - genetics
Risk
Salmon
Sweden - epidemiology
Abstract
Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p
PubMed ID
17066444 View in PubMed
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The association of n-3 fatty acids with serum High Density Cholesterol (HDL) is modulated by sex but not by Inuit ancestry.

https://arctichealth.org/en/permalink/ahliterature118696
Source
Atherosclerosis. 2013 Jan;226(1):281-5
Publication Type
Article
Date
Jan-2013
Author
Peter Bjerregaard
Author Affiliation
Centre for Health Research in Greenland, National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, DK-1353 Copenhagen K, Denmark. pb@niph.dk
Source
Atherosclerosis. 2013 Jan;226(1):281-5
Date
Jan-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Cholesterol, HDL - blood
Fatty Acids, Omega-3 - administration & dosage
Female
Greenland
Humans
Inuits
Male
Middle Aged
Sex Characteristics
Sex Factors
Young Adult
Abstract
To explore the association between dietary n-3 fatty acids and serum lipids in a population with a high intake of marine food. Specifically to test interaction with sex and ethnicity.
Information was obtained from 2280 Inuit who participated in a countrywide health survey in Greenland in 2005-2009. n-3 intake was estimated from an FFQ and analyses of Red Blood Cell (RBC) membranes. Serum total, HDL and LDL cholesterol and triglyceride were analysed. Obesity was measured. Information on ethnicity, smoking, alcohol consumption, and physical activity was obtained from an interview.
In linear regression models adjusted for age, sex, obesity, ethnicity, alcohol, and smoking serum HDL, LDL and triglyceride were associated with n-3 intake estimated as eicosapentaenoic acid (EPA) in RBC membranes. For HDL the interaction between EPA and sex was significant (p 
PubMed ID
23177971 View in PubMed
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Associations between intake of fish and n-3 long-chain polyunsaturated fatty acids and plasma metabolites related to the kynurenine pathway in patients with coronary artery disease.

https://arctichealth.org/en/permalink/ahliterature281604
Source
Eur J Nutr. 2017 Feb;56(1):261-272
Publication Type
Article
Date
Feb-2017
Author
Therese Karlsson
Elin Strand
Jutta Dierkes
Christian A Drevon
Jannike Øyen
Øivind Midttun
Per M Ueland
Oddrun A Gudbrandsen
Eva Ringdal Pedersen
Ottar Nygård
Source
Eur J Nutr. 2017 Feb;56(1):261-272
Date
Feb-2017
Language
English
Publication Type
Article
Keywords
3-Hydroxyanthranilic Acid - metabolism
Aged
Animals
Biomarkers - blood
Body mass index
Cholesterol - blood
Coronary Artery Disease - blood - drug therapy
Cross-Sectional Studies
Energy intake
Fatty Acids, Omega-3 - administration & dosage - blood
Female
Fishes
Humans
Kynurenic Acid - blood
Kynurenine - analogs & derivatives - blood
Male
Middle Aged
Neopterin - blood
Norway
Nutrition Assessment
Seafood
Triglycerides - blood
Tryptophan - blood
Xanthurenates - blood
ortho-Aminobenzoates - blood
Abstract
Enhanced tryptophan degradation via the kynurenine pathway has been related to several pathological conditions. However, little is known about the effect of diet on individual metabolites of this pathway. We investigated cross-sectional associations between reported intake of fish and omega-3 (n-3) long-chain PUFA (LC-PUFA) and plasma metabolites related to the kynurenine pathway.
Participants were 2324 individuals with coronary artery disease from the Western Norway B Vitamin Intervention Trial. Fish and n-3 LC-PUFA intakes were assessed using a food frequency questionnaire. Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, neopterin, and kynurenine-to-tryptophan ratio (KTR) were analyzed. Associations were investigated using partial Spearman's rank correlations and multiple linear regressions.
Median age at inclusion was 62?years (80?% males), and 84?% had stable angina pectoris. Intake of fatty fish and n-3 LC-PUFA was inversely associated with plasma 3-hydroxykynurenine. Consumption of total fish, lean fish, and n-3 LC-PUFA was inversely associated with plasma neopterin. Intake of total fish, fatty fish, and n-3 LC-PUFA was inversely associated with KTR. All these correlations were weak (? between -0.12 and -0.06, P?
PubMed ID
26482150 View in PubMed
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The associations of a marine diet with plasma lipids, blood glucose, blood pressure and obesity among the inuit in Greenland.

https://arctichealth.org/en/permalink/ahliterature4833
Source
Eur J Clin Nutr. 2000 Sep;54(9):732-7
Publication Type
Article
Date
Sep-2000
Author
P. Bjerregaard
H S Pedersen
G. Mulvad
Author Affiliation
National Institute of Public Health, Copenhagen, Denmark. p.bjerregaard@dadlnet.dk
Source
Eur J Clin Nutr. 2000 Sep;54(9):732-7
Date
Sep-2000
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Blood glucose
Blood pressure
Cardiovascular Diseases - blood - ethnology - mortality
Diet
Fatty Acids, Omega-3 - administration & dosage - blood
Female
Greenland - epidemiology
Humans
Inuits
Lipids - blood
Male
Middle Aged
Obesity - epidemiology
Research Support, Non-U.S. Gov't
Risk factors
Seals, Earless
Abstract
OBJECTIVE: To analyse the associations between the intake of fish and marine mammals and risk factors for cardiovascular disease, ie lipid profile, fasting blood glucose, blood pressure and obesity, in a population whose average consumption of n-3 fatty acids is high compared with Western countries. DESIGN: Information was obtained from a population survey in Greenland: interview data, clinical data and fasting blood samples were obtained from a random sample of Inuit from three towns and four villages. SUBJECTS: Two-hundred and fifty-nine adult Inuit (74% of the sample). RESULTS: Marine diet was positively associated with serum high-density lipoprotein (HDL) and blood glucose and inversely with very-low-density lipoprotein (VLDL) and triglyceride. Association with low-density lipoprotein (LDL), diastolic and systolic blood pressure, waist-hip ratio and body mass index were inconsistent and not statistically significant. The pattern was similar within groups with low, medium and high consumption of marine food. CONCLUSIONS: There are statistically significant associations between the consumption of marine food and certain lipid fractions in the blood also in this population with a very high average intake of marine food. The observation that blood glucose is positively associated with marine diet in a population survey is new and should be repeated. There was good agreement between the results for the reported consumption of seal and those for the biomarkers. SPONSORSHIP: The study was financially supported by the Greenland Home Rule, Directorate of Health and Research, the Commission for Scientific Research in Greenland, and the Danish Medical Research Council.
PubMed ID
11002386 View in PubMed
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Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with heart rate-corrected QT and JT intervals in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

https://arctichealth.org/en/permalink/ahliterature294365
Source
Eur J Nutr. 2017 Oct; 56(7):2319-2327
Publication Type
Journal Article
Date
Oct-2017
Author
Behnam Tajik
Sudhir Kurl
Tomi-Pekka Tuomainen
Jyrki K Virtanen
Author Affiliation
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, PO Box 1627, 70211, Kuopio, Finland.
Source
Eur J Nutr. 2017 Oct; 56(7):2319-2327
Date
Oct-2017
Language
English
Publication Type
Journal Article
Keywords
Adult
Animals
Arrhythmias, Cardiac - blood - epidemiology
Death, Sudden, Cardiac - epidemiology
Fatty Acids, Omega-3 - administration & dosage - blood
Finland
Fishes
Follow-Up Studies
Hair - chemistry
Heart rate
Humans
Male
Mercury - analysis
Middle Aged
Prospective Studies
Risk factors
Seafood - analysis
Abstract
Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been associated with risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Mercury exposure, mainly due fish consumption, has been associated with higher risk. However, the impact of PUFAs or mercury on the ventricular cardiac arrhythmias, which often precede SCD, is not completely known. We investigated the associations of the serum long-chain omega-3 PUFAs and hair mercury with ventricular repolarization, measured by heart rate-corrected QT and JT intervals (QTc and JTc, respectively).
A total of 1411 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD in 1984-1989, were studied.
Serum long-chain omega-3 PUFA concentrations were inversely associated with QTc and JTc (multivariate-adjusted P trend across quartiles = 0.02 and 0.002, respectively) and, during the mean 22.9-year follow-up, with lower SCD risk. However, further adjustments for QTc, JTc or hair mercury did not attenuate the associations with SCD. Hair mercury was not associated with QTc, JTc or SCD risk, but it slightly attenuated the associations of the serum long-chain omega-3 PUFA with QTc and JTc.
Higher serum long-chain omega-3 PUFA concentrations, mainly a marker for fish consumption, were inversely associated with QTc and JTc in middle-aged and older men from Eastern Finland, but QTc or JTc did not attenuate the inverse associations of the long-chain omega-3 PUFA with SCD risk. This suggests that prevention of prolonged ventricular repolarization may not explain the inverse association of the long-chain omega-3 PUFA with SCD risk.
Notes
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PubMed ID
27431893 View in PubMed
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Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults.

https://arctichealth.org/en/permalink/ahliterature157100
Source
Diabetologia. 2008 Jul;51(7):1261-8
Publication Type
Article
Date
Jul-2008
Author
A. Ramel
A. Martinéz
M. Kiely
G. Morais
N M Bandarra
I. Thorsdottir
Author Affiliation
Landspitali-University Hospital & Faculty of Food Science and Nutrition, Eiriksgata 29, 101, Reykjavik, Iceland.
Source
Diabetologia. 2008 Jul;51(7):1261-8
Date
Jul-2008
Language
English
Publication Type
Article
Keywords
Adiponectin - blood
Adult
Diet, Reducing
Dietary Fats - administration & dosage
Energy Metabolism
European Continental Ancestry Group
Fatty Acids, Omega-3 - administration & dosage
Female
Fish Oils - administration & dosage
Homeostasis - physiology
Humans
Iceland
Insulin Resistance - physiology
Male
Obesity - diet therapy - metabolism
Overweight - diet therapy - metabolism
Seafood
Treatment Outcome
Triglycerides - blood
Abstract
Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction.
In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group.
Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements.
LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin.
ClinicalTrials.gov NCT00315770.
PubMed ID
18491071 View in PubMed
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Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?

https://arctichealth.org/en/permalink/ahliterature3153
Source
Prostaglandins Leukot Essent Fatty Acids. 2000 Dec;63(6):351-62
Publication Type
Article
Date
Dec-2000
Author
U N Das
Author Affiliation
EFA Sciences LLC, 1420 Providence Highway, Norwood, MA 02062, USA. undurti@hotmail.com
Source
Prostaglandins Leukot Essent Fatty Acids. 2000 Dec;63(6):351-62
Date
Dec-2000
Language
English
Publication Type
Article
Keywords
Acetylcholine - physiology
Animals
Arrhythmia - epidemiology - prevention & control
Brain - physiopathology
Cardiovascular Diseases - diet therapy - epidemiology - prevention & control
Cell Adhesion Molecules - biosynthesis - genetics
Cell Division - drug effects
Clinical Trials
Cohort Studies
Cytokines - metabolism
Dietary Fats - administration & dosage - pharmacology - therapeutic use
Eicosanoids - metabolism
Endothelium, Vascular - drug effects - metabolism
Exercise
Fatty Acids, Omega-3 - administration & dosage - pharmacology - therapeutic use
Fatty Acids, Unsaturated - metabolism
Fish Oils - administration & dosage - pharmacology - therapeutic use
Gene Expression Regulation - drug effects
Greenland - epidemiology
Heart - drug effects
Hemostasis - drug effects
Humans
Hypothalamo-Hypophyseal System - drug effects - physiopathology
Inflammation - drug therapy - metabolism - prevention & control
Inuits
Japan - epidemiology
Lipid Metabolism
Models, Biological
Myocardium - metabolism
Oxidation-Reduction
Oxidative Stress
Parasympathetic Nervous System - drug effects
Pituitary-Adrenal System - drug effects - physiopathology
Rats
Sodium Channels - drug effects
Vagus Nerve - physiopathology
Abstract
Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
Notes
Erratum In: Prostaglandins Leukot Essent Fatty Acids 2001 Jan;64(1):74
PubMed ID
11133172 View in PubMed
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CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik people.

https://arctichealth.org/en/permalink/ahliterature259143
Source
J Diabetes. 2014 May;6(3):251-9
Publication Type
Article
Date
May-2014
Author
Yann C Klimentidis
Dominick J Lemas
Howard H Wiener
Diane M O'Brien
Peter J Havel
Kimber L Stanhope
Scarlett E Hopkins
Hemant K Tiwari
Bert B Boyer
Source
J Diabetes. 2014 May;6(3):251-9
Date
May-2014
Language
English
Publication Type
Article
Keywords
Adult
Alaska - epidemiology
Blood Glucose - metabolism
Body mass index
Cyclin-Dependent Kinase 5 - genetics
Diabetes Mellitus, Type 2 - blood - ethnology - genetics
Diet
Fasting - blood
Fatty Acids, Omega-3 - administration & dosage
Female
Gene Frequency
Genetic Predisposition to Disease - ethnology - genetics
Genotype
Hemoglobin A, Glycosylated - metabolism
Homeodomain Proteins - genetics
Humans
Insulin - blood
Inuits - genetics
Linear Models
Male
Middle Aged
Polymorphism, Single Nucleotide
Prevalence
Risk factors
Transcription Factors - genetics
Young Adult
Abstract
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations.
In 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score (GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index (BMI), and n-3 PUFA intake.
The rs7754840 SNP in CDKAL1 is significantly associated with HbA1c (P?=?0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose (FG) and HbA1c measure (P?=?0.00046) and with homeostatic model assessment of ?-cell function (HOMA-B; P?=?0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEX SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake.
Our results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.
PubMed ID
24112421 View in PubMed
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