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Association of a genetic variant in the AKT gene locus and cardiovascular risk factors
Corresponding Author(s) : Farnoush Kermanshahi
Cellular and Molecular Biology,
Vol. 66 No. 3: Issue 3
Abstract
Cardiovascular disease (CVDs) is the leading cause of morbidity and death worldwide. Most genetic variants could be identified by several genome-wide-association-studies (GWAS), including within genes encoding proteins involved in the AKT/PI3K pathways that are related with an increased risk of metabolic syndrome and CVDs. Therefore, due to the importance of genetic variants in the prognosis of diseases, we examined the genetic polymorphism of AKT-rs1130233 located on chromosome 14 with cardiovascular risk factors. In this cross-sectional study, 721 subjects recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort study. The participants including 257 subjects with metabolic syndrome, 144 subjects with cardiovascular disease and 320 subjects as a control group. Anthropometric, biochemical and demographic information measures were prepared. Dietary assessment was managed by 24h dietary recall. DNA extraction and genotyping were carried out by using the TaqMan real-time-PCR based method. The association of AKT rs1130233 locus with dietary intakes, metabolic syndrome and cardiovascular risk factors were assessed. Data were analyzed by using SPSS 21 software. Frequencies of genotypes AA, AG and GG of the AKT rs1130233 polymorphism were 12.6%, 44.5% and 42.9% in subjects with metabolic syndrome and 9.7%, 39.6% and 50.7% in subjects with cardiovascular disease, respectively. The frequency of allele A and G in cardiovascular disease and metabolic syndrome population were 29.5%, 70.5% and 34.8%, 65.2%, respectively. We have found no significant association between the AKT rs1130233 polymorphism with cardiovascular risk factors and metabolic syndrome. The results of dietary intake showed that the levels of phosphorus intake (p=0.008), calcium intake (p=0.007) and iodine intake (p=0.04) were different in subjects with and without metabolic syndrome. And also, energy intake was significantly different in subjects with cardiovascular disease (p=0.01) compared to the control group. Our findings suggest that AKT rs1130233 was not associated with the risk of metabolic syndrome and cardiovascular disease in the Iranian population. More studies are needed to validate our results. We did functional analysis, due to certify our investigation about value of this genetic biomarker for CVD risk.
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- Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. CIRC J. 2005;112(17):2735-52.
- Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. CIRC J. 2005;112(20):3066-72.
- Azizi F, Rahmani M, Emami H, Mirmiran P, Hajipour R, Madjid M, et al. Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1). SOZ PRAVENTIV MED. 2002;47(6):408-26.
- Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch. Intern. Med. 2004;164(10):1066-76.
- Alberti K, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. CIRC J. 2009;120(16):1640-5.
- Zimmet P, Alberti K, Shaw J. International Diabetes Federation: the IDF consensus worldwide definition of the metabolic syndrome. Diabetes voice. 2005;50:31-3.
- Mazloomzadeh S, Khazaghi ZR, Mousavinasab N. The prevalence of metabolic syndrome in Iran: a systematic review and meta-analysis. IRAN J PUBLIC HEALTH. 2018;47(4):473.
- Ahmadnezhad M, Asadi Z, Miri HH, Ferns GA, Ghayour-Mobarhan M, Ebrahimi-Mamaghani M. Validation of a Short Semi-Quantitative Food Frequency Questionnaire for Adults: a Pilot study. Journal of Nutritional Sciences and Dietetics. 2017.
- Ghazizadeh H, Avan A, Fazilati M, Azimi-Nezhad M, Tayefi M, Ghasemi F, et al. Association of rs6921438 A< G with serum vascular endothelial growth factor concentrations in patients with metabolic syndrome. Gene. 2018;667:70-5.
- Ghazizadeh H, Fazilati M, Pasdar A, Avan A, Tayefi M, Ghasemi F, et al. Association of a vascular endothelial growth factor genetic variant with serum VEGF level in subjects with metabolic syndrome. Gene. 2017;598:27-31.
- Sakowicz A, Stć™pniak D, Hejduk P, Pietrucha T. The genetics of metabolic syndrome. Med Sci Technol. 2013;54:48-53.
- Groop L. Genetics of the metabolic syndrome. Br. J. Nutr. 2000;83(S1): S39-S48.
- Wu Y, Yu Y, Zhao T, Wang S, Fu Y, Qi Y, et al. Interactions of environmental factors and APOA1-APOC3-APOA4-APOA5 gene cluster gene polymorphisms with metabolic syndrome. PLoS One. 2016;11(1).
- Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nature Reviews Cancer. 2009;9(8):550-62.
- Staal SP, Huebner K, Croce CM, Parsa NZ, Testa JR. The AKT1 proto-oncogene maps to human chromosome 14, band q32. Genomics. 1988;2(1):96-8.
- Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ). Science. 2001;292(5522):1728-31.
- Zhuravleva E, Tschopp O, Hemmings BA. Role of PKB/Akt in liver diseases. Signaling Pathways in Liver Diseases: Springer; 2010. p. 243-59.
- Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. CELL SIGNAL. 2011;23(10):1515-27.
- Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. AM J PHYSIOL-HEART C. 2005;289(2): H813-H22.
- Karnehed N, Tynelius P, Heitman BL, Rasmussen F. Physical activity, diet and gene-environment interactions in relation to body mass index and waist circumference: the Swedish young male twins study. Public Health Nutr. 2006;9(7):851-8.
- Ghayour-Mobarhan M, Moohebati M, Esmaily H, Ebrahimi M, Parizadeh SMR, Heidari-Bakavoli AR, et al. Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation. Int. J. Public Health. 2015;60(5):561-72.
- Alberti KGM, Zimmet P, Shaw J. The metabolic syndrome”a new worldwide definition. The Lancet. 2005;366(9491):1059-62.
- Hedayatnia M, Asadi Z, Zare-Feyzabadi R, Yaghooti-Khorasani M, Ghazizadeh H, Ghaffarian-Zirak R, et al. Dyslipidemia and cardiovascular disease risk among the MASHAD study population. LIPIDS HEALTH DIS. 2020;19(1):1-11.
- Motamed S, Ebrahimi M, Safarian M, Ghayour-Mobarhan M, Mouhebati M, Azarpazhouh M, et al. Micronutrient intake and the presence of the metabolic syndrome. N Am J Med Sci. 2013;5(6):377.
- Avan A, Avan A, Le Large TY, Mambrini A, Funel N, Maftouh M, et al. AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. PloS one. 2014;9(9).
- Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. The AM J CLIN NUTR. 1997;65(4):1220S-8S.
- Barati E, Ghazizadeh H, Sadabadi F, Kazemi E, Ferns GA, Avan A, et al. Association of the IL6 gene polymorphism with component features of metabolic syndrome in obese subjects. BIGI. 2019;57(5):695-708.
- Eshaghi FS, Ghazizadeh H, Kazami-Nooreini S, Timar A, Esmaeily H, Mehramiz M, et al. Association of a genetic variant in AKT1 gene with features of the metabolic syndrome. Genes & Diseases. 2019;6(3):290-5.
- Lin H-F, Boden-Albala B, Juo S, Park N, Rundek T, Sacco RL. Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia. 2005;48(10):2006-12.
- Povel C, Boer J, Reiling E, Feskens E. Genetic variants and the metabolic syndrome: a systematic review. OBES REV. 2011;12(11):952-67.
- Taheri M, Yousefi K, Naderi M, Hashemi M. Genetic Variation in Akt1 and Risk of Tuberculosis Among Iranian Population. 2014; 0-0.
- Bizhani F, Hashemi M, Danesh H, Nouralizadeh A, Narouie B, Bahari G, et al. Association between single nucleotide polymorphisms in the PI3K/AKT/mTOR pathway and bladder cancer risk in a sample of Iranian population. EXCLI J. 2018;17:3.
- Yi J, Lee K, Joo E, Kim Y. 180–Failure to support an association between AKT1 gene and schizophrenia in Korean population. Schizophr. Res. 2008 (98):107.
- Piao Y, Li Y, Xu Q, Liu J-w, Xing C-z, Xie X-d, et al. Association of MTOR and AKT gene polymorphisms with susceptibility and survival of gastric cancer. PloS one. 2015;10(8).
- Asadi Z, Shafiee M, Sadabadi F, Saberi-Karimian M, Darroudi S, Tayefi M, et al. Association Between dietary patterns and the risk of metabolic syndrome among Iranian population: A cross-sectional study. Diabetes Metab Syndr: Clinical Research & Reviews. 2019;13(1):858-65.
- Kharazmi-Khorassani S, Kharazmi-Khorassani J, Rastegar-Moghadam A, Samadi S, Ghazizadeh H, Tayefi M, et al. Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome. BMC MED GENET. 2019;20(1):97.
- Ghassemi H, Harrison G, Mohammad K. An accelerated nutrition transition in Iran. Public Health Nutr. 2002;5(1a):149-55.
- Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2009;32(4):688-94.
- Wyshak G, Frisch RE. Carbonated beverages, dietary calcium, the dietary calcium/phosphorus ratio, and bone fractures in girls and boys. J ADOLESCENT HEALTH. 1994;15(3):210-5.
- Smilowitz JT, Wiest MM, Teegarden D, Zemel MB, German JB, Van Loan MD. Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial. NUTR METAB. 2011;8(1):67.
- Kirii K, Mizoue T, Iso H, Takahashi Y, Kato M, Inoue M, et al. Calcium, vitamin D and dairy intake in relation to type 2 diabetes risk in a Japanese cohort. Diabetologia. 2009;52(12):2542-50.
- Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older US women. Diabetes Care. 2005;28(12):2926-32.
- Cavero-Redondo I, Alvarez-Bueno C, Sotos-Prieto M, Gil A, Martinez-Vizcaino V, Ruiz JR. Milk and dairy product consumption and risk of mortality: An overview of systematic reviews and meta-analyses. ADV NUTR. 2019;10(suppl_2):S97-S104.
- Abargouei AS, Janghorbani M, Salehi-Marzijarani M, Esmaillzadeh A. Effect of dairy consumption on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Int J Obes. 2012;36(12):1485-93.
- Mohammadi SG, Mirmiran P, Bahadoran Z, Mehrabi Y, Azizi F. The association of dairy intake with metabolic syndrome and its components in adolescents: Tehran Lipid and Glucose Study. Int J Endocrinol Metab. 2015;13(3).
- Mohammadifard N, Akhavan-Tabib A, Sajjadi F, Alikhasi H, Taheri M, Khani A, et al. Dairy products and metabolic syndrome among Iranian adult population: Isfahan Healthy Heart Program. Int. Dairy J. 2020;105:104667.
- Hoffmann IS, Cubeddu LX. Salt and the metabolic syndrome. NUTR METAB CARDIOVAS. 2009;19(2):123-8.
- Andersson M, De Benoist B, Darnton-Hill I, Delange F. Iodine deficiency in Europe: a continuing public health problem: World Health Organization Geneva; 2007.
- Shim J-S, Oh K, Kim HC. Dietary assessment methods in epidemiologic studies. Epidemiol Health. 2014;36.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
References
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. CIRC J. 2005;112(17):2735-52.
Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. CIRC J. 2005;112(20):3066-72.
Azizi F, Rahmani M, Emami H, Mirmiran P, Hajipour R, Madjid M, et al. Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1). SOZ PRAVENTIV MED. 2002;47(6):408-26.
Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch. Intern. Med. 2004;164(10):1066-76.
Alberti K, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. CIRC J. 2009;120(16):1640-5.
Zimmet P, Alberti K, Shaw J. International Diabetes Federation: the IDF consensus worldwide definition of the metabolic syndrome. Diabetes voice. 2005;50:31-3.
Mazloomzadeh S, Khazaghi ZR, Mousavinasab N. The prevalence of metabolic syndrome in Iran: a systematic review and meta-analysis. IRAN J PUBLIC HEALTH. 2018;47(4):473.
Ahmadnezhad M, Asadi Z, Miri HH, Ferns GA, Ghayour-Mobarhan M, Ebrahimi-Mamaghani M. Validation of a Short Semi-Quantitative Food Frequency Questionnaire for Adults: a Pilot study. Journal of Nutritional Sciences and Dietetics. 2017.
Ghazizadeh H, Avan A, Fazilati M, Azimi-Nezhad M, Tayefi M, Ghasemi F, et al. Association of rs6921438 A< G with serum vascular endothelial growth factor concentrations in patients with metabolic syndrome. Gene. 2018;667:70-5.
Ghazizadeh H, Fazilati M, Pasdar A, Avan A, Tayefi M, Ghasemi F, et al. Association of a vascular endothelial growth factor genetic variant with serum VEGF level in subjects with metabolic syndrome. Gene. 2017;598:27-31.
Sakowicz A, Stć™pniak D, Hejduk P, Pietrucha T. The genetics of metabolic syndrome. Med Sci Technol. 2013;54:48-53.
Groop L. Genetics of the metabolic syndrome. Br. J. Nutr. 2000;83(S1): S39-S48.
Wu Y, Yu Y, Zhao T, Wang S, Fu Y, Qi Y, et al. Interactions of environmental factors and APOA1-APOC3-APOA4-APOA5 gene cluster gene polymorphisms with metabolic syndrome. PLoS One. 2016;11(1).
Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nature Reviews Cancer. 2009;9(8):550-62.
Staal SP, Huebner K, Croce CM, Parsa NZ, Testa JR. The AKT1 proto-oncogene maps to human chromosome 14, band q32. Genomics. 1988;2(1):96-8.
Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ). Science. 2001;292(5522):1728-31.
Zhuravleva E, Tschopp O, Hemmings BA. Role of PKB/Akt in liver diseases. Signaling Pathways in Liver Diseases: Springer; 2010. p. 243-59.
Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. CELL SIGNAL. 2011;23(10):1515-27.
Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. AM J PHYSIOL-HEART C. 2005;289(2): H813-H22.
Karnehed N, Tynelius P, Heitman BL, Rasmussen F. Physical activity, diet and gene-environment interactions in relation to body mass index and waist circumference: the Swedish young male twins study. Public Health Nutr. 2006;9(7):851-8.
Ghayour-Mobarhan M, Moohebati M, Esmaily H, Ebrahimi M, Parizadeh SMR, Heidari-Bakavoli AR, et al. Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation. Int. J. Public Health. 2015;60(5):561-72.
Alberti KGM, Zimmet P, Shaw J. The metabolic syndrome”a new worldwide definition. The Lancet. 2005;366(9491):1059-62.
Hedayatnia M, Asadi Z, Zare-Feyzabadi R, Yaghooti-Khorasani M, Ghazizadeh H, Ghaffarian-Zirak R, et al. Dyslipidemia and cardiovascular disease risk among the MASHAD study population. LIPIDS HEALTH DIS. 2020;19(1):1-11.
Motamed S, Ebrahimi M, Safarian M, Ghayour-Mobarhan M, Mouhebati M, Azarpazhouh M, et al. Micronutrient intake and the presence of the metabolic syndrome. N Am J Med Sci. 2013;5(6):377.
Avan A, Avan A, Le Large TY, Mambrini A, Funel N, Maftouh M, et al. AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. PloS one. 2014;9(9).
Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. The AM J CLIN NUTR. 1997;65(4):1220S-8S.
Barati E, Ghazizadeh H, Sadabadi F, Kazemi E, Ferns GA, Avan A, et al. Association of the IL6 gene polymorphism with component features of metabolic syndrome in obese subjects. BIGI. 2019;57(5):695-708.
Eshaghi FS, Ghazizadeh H, Kazami-Nooreini S, Timar A, Esmaeily H, Mehramiz M, et al. Association of a genetic variant in AKT1 gene with features of the metabolic syndrome. Genes & Diseases. 2019;6(3):290-5.
Lin H-F, Boden-Albala B, Juo S, Park N, Rundek T, Sacco RL. Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia. 2005;48(10):2006-12.
Povel C, Boer J, Reiling E, Feskens E. Genetic variants and the metabolic syndrome: a systematic review. OBES REV. 2011;12(11):952-67.
Taheri M, Yousefi K, Naderi M, Hashemi M. Genetic Variation in Akt1 and Risk of Tuberculosis Among Iranian Population. 2014; 0-0.
Bizhani F, Hashemi M, Danesh H, Nouralizadeh A, Narouie B, Bahari G, et al. Association between single nucleotide polymorphisms in the PI3K/AKT/mTOR pathway and bladder cancer risk in a sample of Iranian population. EXCLI J. 2018;17:3.
Yi J, Lee K, Joo E, Kim Y. 180–Failure to support an association between AKT1 gene and schizophrenia in Korean population. Schizophr. Res. 2008 (98):107.
Piao Y, Li Y, Xu Q, Liu J-w, Xing C-z, Xie X-d, et al. Association of MTOR and AKT gene polymorphisms with susceptibility and survival of gastric cancer. PloS one. 2015;10(8).
Asadi Z, Shafiee M, Sadabadi F, Saberi-Karimian M, Darroudi S, Tayefi M, et al. Association Between dietary patterns and the risk of metabolic syndrome among Iranian population: A cross-sectional study. Diabetes Metab Syndr: Clinical Research & Reviews. 2019;13(1):858-65.
Kharazmi-Khorassani S, Kharazmi-Khorassani J, Rastegar-Moghadam A, Samadi S, Ghazizadeh H, Tayefi M, et al. Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome. BMC MED GENET. 2019;20(1):97.
Ghassemi H, Harrison G, Mohammad K. An accelerated nutrition transition in Iran. Public Health Nutr. 2002;5(1a):149-55.
Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2009;32(4):688-94.
Wyshak G, Frisch RE. Carbonated beverages, dietary calcium, the dietary calcium/phosphorus ratio, and bone fractures in girls and boys. J ADOLESCENT HEALTH. 1994;15(3):210-5.
Smilowitz JT, Wiest MM, Teegarden D, Zemel MB, German JB, Van Loan MD. Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial. NUTR METAB. 2011;8(1):67.
Kirii K, Mizoue T, Iso H, Takahashi Y, Kato M, Inoue M, et al. Calcium, vitamin D and dairy intake in relation to type 2 diabetes risk in a Japanese cohort. Diabetologia. 2009;52(12):2542-50.
Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older US women. Diabetes Care. 2005;28(12):2926-32.
Cavero-Redondo I, Alvarez-Bueno C, Sotos-Prieto M, Gil A, Martinez-Vizcaino V, Ruiz JR. Milk and dairy product consumption and risk of mortality: An overview of systematic reviews and meta-analyses. ADV NUTR. 2019;10(suppl_2):S97-S104.
Abargouei AS, Janghorbani M, Salehi-Marzijarani M, Esmaillzadeh A. Effect of dairy consumption on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Int J Obes. 2012;36(12):1485-93.
Mohammadi SG, Mirmiran P, Bahadoran Z, Mehrabi Y, Azizi F. The association of dairy intake with metabolic syndrome and its components in adolescents: Tehran Lipid and Glucose Study. Int J Endocrinol Metab. 2015;13(3).
Mohammadifard N, Akhavan-Tabib A, Sajjadi F, Alikhasi H, Taheri M, Khani A, et al. Dairy products and metabolic syndrome among Iranian adult population: Isfahan Healthy Heart Program. Int. Dairy J. 2020;105:104667.
Hoffmann IS, Cubeddu LX. Salt and the metabolic syndrome. NUTR METAB CARDIOVAS. 2009;19(2):123-8.
Andersson M, De Benoist B, Darnton-Hill I, Delange F. Iodine deficiency in Europe: a continuing public health problem: World Health Organization Geneva; 2007.
Shim J-S, Oh K, Kim HC. Dietary assessment methods in epidemiologic studies. Epidemiol Health. 2014;36.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.