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Klotho gen metilasyon seviyesi ile diyet alışkanlığı arasındaki ilişki

Year 2024, Volume: 49 Issue: 4, 965 - 973, 30.12.2024
https://doi.org/10.17826/cumj.1551174

Abstract

Amaç: Bu çalışma, Klotho geninin metilasyon seviyesi ile beslenme alışkanlıkları arasındaki ilişkiyi belirlemeyi amaçlamıştır.
Gereç ve Yöntem: Sağlıklı bir örnek grubumuzdan oluşan 20 kişiden iki grup oluşturulmuştur: 10 kişi karbonhidratlarla beslenen ve 10 kişi proteinle beslenen. İlk olarak, bireylere bir gıda tüketim sıklığı belirleme formu anket olarak uygulanmıştır. Bu anketin sonuçlarına dayanarak, katılımcıların tükettikleri gıda miktarları (g/cc) belirlenmiştir. Anket bulgularına göre, iki grup oluşturulmuştur: karbonhidrat tüketicileri olarak sınıflandırılanlar (besinlerinin %33'ünü veya daha fazlasını karbonhidratlardan alan bireyler) ve protein tüketicileri olarak sınıflandırılanlar (besinlerinin %17'sini veya daha fazlasını proteinlerden alan bireyler). Bireylerin kan örneklerinde Klotho geninin metilasyon seviyeleri; DNA izolasyonu, RT-PCR ve Bisülfit Modifikasyonu ile incelenmiştir.
Bulgular: Karbonhidrat diyeti grubunda; yağ ve metilasyon yüzdeleri arasında çok güçlü ve ters bir korelasyon vardı (r = -0,765, p = 0,05). Karbonhidrat ve metilasyon yüzdeleri arasında güçlü bir korelasyon vardı (r = 0,778, p = 0,004). BMI ile metilasyon yüzdesi arasında da güçlü bir korelasyon bulundu (r = 0,712, p = 0,01). Kolesterol ile metilasyon yüzdeleri arasında güçlü bir ters korelasyon vardı (r = -0,556, p = 0,04). Protein diyeti grubunda, BMI ile metilasyon arasında güçlü bir ters korelasyon vardı (r = -0,635, p = 0,024).
Sonuç: Analiz sonuçlarına göre, karbonhidrat temelli beslenen bireylerde Klotho geninin metilasyon yüzdesinin (%33) protein temelli beslenen bireylerden (%17) daha yüksek olduğu bulunmuştur. Elde edilen veriler, karbonhidrat tüketimi arttıkça Klotho geninin metilasyon seviyesinin de yükseldiğini göstermektedir.

Ethical Statement

Decision numbered 2018/1279 was taken on 16.03.2018 at the 65th meeting.

Supporting Institution

This research was supported by Necmettin Erbakan University Scientific Research Projects Coordination with project number 181318008.

Thanks

This research was supported by Necmettin Erbakan University Scientific Research Projects Coordination with project number 181318008.

References

  • Aczel D, Torma F, Jokai M, McGreevy K, Boros A, Seki Y et al. The circulating level of Klotho is not dependent upon physical fitness and age-associated methylation increases at the promoter region of the Klotho gene. Genes (Basel). 2023;14:525.
  • McLachlan KJJ, Cole JH, Harris SE, Marioni RE, Deary IJ, Gale CR. Attitudes to ageing, biomarkers of ageing and mortality: The Lothian Birth Cohort 1936. J Epidemiol Community Health. 2020;74:377-83.
  • Salameh Y, Bejaoui Y, El Hajj N. DNA methylation biomarkers in aging and age-related diseases. Front Genet. 2020;11:480672.
  • Kuro M. Klotho and calciprotein particles as therapeutic targets against accelerated ageing. Clin Sci. 2021;135:1915-27.
  • Fung TY, Iyaswamy A, Sreenivasmurthy SG, Krishnamoorthi S, Guan XJ, Zhu Z et al. Klotho an autophagy stimulator as a potential therapeutic target for Alzheimer’s disease: a review. Biomedicines. 2022;10.3:705.
  • Kuro-o M. The Klotho proteins in health and disease. Nat Rev Nephrol. 2019;15:27-44.
  • Razzaque MS. Is Klotho an essential player? Am J Physiol Renal Physiol. 2009;296:470-6.
  • Wu SE, Chen YJ, Chen WL. Adherence to Mediterranean diet and soluble Klotho level: the value of food synergy in aging. Nutrients. 2022;14:3910.
  • Dhar GA, Saha S, Mitra P, Nag Chaudhuri R. DNA methylation and regulation of gene expression: guardian of our health. Nucleus (India). 2021;64:259-70.
  • Bond DM, Finnegan EJ. Passing the message on: inheritance of epigenetic traits. Trends Plant Sci. 2007;12:211-6.
  • Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88.
  • Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38:23-38.
  • Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev. 2021;69:101348.
  • Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102.30:10604-9.
  • Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015;14:924-32.
  • Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA. 2012;109:10522-7.
  • Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA. 2006;103.5:1412-7.
  • Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39:457-66.
  • Cortessis VK, Thomas DC, Joan Levine A, Breton C V, Mack TM, Siegmund KD et al. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 2012;131:1565-89.
  • Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13:97-109.
  • Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP et al. Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem. 2006;281:6120-3.
  • Guarnotta V, Pizzolanti G, Petrancosta R, Radellini S, Baiamonte C, Giordano C. Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case–control study. J Endocrinol Invest. 2022;45:1247-54.
  • Drew DA, Katz R, Kritchevsky S, Ix JH, Shlipak MG, Newman AB et al. Soluble Klotho and incident hypertension. Clin J Am Soc Nephrol. 2021;16:1502-11.
  • Donate-Correa J, Ferri CM, Martín-Núñez E, Pérez-Delgado N, González-Luis A, Mora-Fernández C et al. Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease. Sci Rep. 2021;11:15877.
  • Buendia-Roldan I, Machuca N, Mejía M, Maldonado M, Pardo A, Selman M. Lower levels of α-Klotho in serum are associated with decreased lung function in individuals with interstitial lung abnormalities. Sci Rep. 2019;9:10801.
  • Corcillo A, Fountoulakis N, Sohal A, Farrow F, Ayis S, Karalliedde J. Low levels of circulating anti-ageing hormone Klotho predict the onset and progression of diabetic retinopathy. Diab Vasc Dis Res. 2020;17:1479164120970901.
  • Paroni G, Panza F, De Cosmo S, Greco A, Seripa D, Mazzoccoli G. Klotho at the edge of Alzheimer’s disease and senile depression. Mol Neurobiol. 2019;56:1908-20.
  • Izquierdo MC, Perez-Gomez MV, Sanchez-Niño MD, Sanz AB, Ruiz-Andres O, Poveda J et al. Klotho, phosphate and inflammation/ageing in chronic kidney disease. Nephrol Dial Transplant. 2012;27:suppl4:iv6-10.
  • Liu P, Wang Y, Yang G, Zhang Q, Meng L, Xin Y et al. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol Res. 2021;165:105420.
  • Orces CH. The association of obesity and the antiaging humoral factor Klotho among adults in the United States. J Am Coll Nutr. 2019;38:683-9.
  • Zhang H, Shi Y, Ma F, Wang L, Hou Y, Zhu, Z. Association of Klotho single nucleotide polymorphisms with cardiovascular diseases: a systematic review and meta-analysis. Int J Clin Exp Med. 2017;10:5721-41.
  • Hikone K, Hasegawa T, Tsuchiya E, Hongo H, Sasaki M, Yamamoto T et al. Histochemical examination on periodontal tissues of Klotho-deficient mice fed with phosphate-insufficient diet. J Histochem Cytochem. 2017;65:207-21.
  • Maekawa R, Seino Y, Ogata H, Murase M, Iida A, Hosokawa K et al. Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice. J Nutr Biochem. 2017;49:71-9.
  • Wilkens MR, Elfers K, Schmicke M, Breves G, Muscher-Banse AS. Dietary nitrogen and calcium modulate CYP27B1 expression in young goats. Domest Anim Endocrinol. 2018;64:70-6.
  • Milovanova SYu, Milovanov YuS, Taranova M V, Dobrosmyslov IA. Effects of keto/amino acids and a low-protein diet on the nutritional status of patients with stages 3B-4 chronic kidney disease. Ter Arkh. 2017;89:30-3.
  • Zapata RC, Singh A, Pezeshki A, Avirineni BS, Patra S, Chelikani PK. Low‐protein diets with fixed carbohydrate content promote hyperphagia and sympathetically mediated increase in energy expenditure. Mol Nutr Food Res. 2019;63:1900088.
  • Shafie A, Rahimi AM, Ahmadi I, Nabavizadeh F, Ranjbaran M, Ashabi G. High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats’ brain: the toxic role of high-fat diet. Nutr Metab (Lond). 2020;17:86.
  • dos Santos MS, Canale D, Bernardo DRD, Shimizu MHM, Seguro AC, Volpini RA et al. The restoration of vitamin D levels slows the progression of renal ischemic injury in rats previously deficient in vitamin D. Front Med (Lausanne). 2021;8:625647.
  • Hu MC, Kuro-o M, Moe OW. Renal and extrarenal actions of Klotho. Semin Nephrol. 2013;33:118-29.
  • Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF et al. Klotho allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet. 2003;72:1154-61.
  • Ogata N, Matsumura Y, Shiraki M, Kawano K, Koshizuka Y, Hosoi T et al. Association of Klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women. Bone. 2002;31:37-42.
  • Sachdeva A, Gouge J, Kontovounisios C, Nikolaou S, Ashworth A, Lim K et al. Klotho and the treatment of human malignancies. Cancers (Basel). 2020;12:1665.
  • Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012;81:640-50.
  • Kulis M, Esteller M. DNA methylation and cancer. In: Epigenetic Alterations in Oncogenesis (Ed J Tost):27-56. London, Elsevier, 2010.
  • Huang Y, Xu Q, Liu M. Dietary carbohydrates and their impact on DNA methylation: Implications for health. Nutr Neurosci. 2015;18:23-30.
  • Agudo-Lopez A, Miguel BG, Fernandez I, Martinez AM, Araki S, Dobashi K et al. Dietary patterns and DNA methylation in aging and longevity: A cross-sectional study. BMC Geriatr. 2016;16:54

Relationship between Klotho gene methylation level and diet habit

Year 2024, Volume: 49 Issue: 4, 965 - 973, 30.12.2024
https://doi.org/10.17826/cumj.1551174

Abstract

Purpose: This study aimed to determine the relationship between the methylation level of the Klotho gene and nutritional habits.
Materials and Methods: From our healthy sample group consisting of 20 people, two groups were created: 10 people fed with carbohydrates and 10 people had protein. Initially, a food consumption frequency determination form was administered as a survey to individuals. Based on the results of this survey, the amounts of food consumed by the participants (g/cc) were determined. According to the findings of the survey, two groups were formed: those classified as carbohydrate consumers (individuals consuming 33% or more of their diet from carbohydrates) and those classified as protein consumers (individuals consuming 17% or more of their diet from protein). Methylation level of Klotho gene in blood samples of individuals; DNA isolation, RT-PCR and Bisulfite Modification were examined.
Results: In the carbohydrate diet group; there was a very strong and inverse correlation between fat and methylation percentages (r = -0.765, p = 0.05). There was a strong correlation between the percentages of carbohydrate and methylation (r = 0.778, p = 0.004). A strong correlation was also found between BMI and methylation percentage (r = 0.712, p = 0.01). There was a strong inverse correlation between cholesterol and methylation percentages (r =-0.556, p = 0.04). In the protein diet group, there was a strong inverse correlation between BMI and methylation (r =-0.635, p = 0.024).
Conclusion: As a result of the analysis, the Klotho gene methylation percentage (33%) in individuals with a carbohydrate-based diet was found to be higher than that in individuals with a protein-based diet (17%). The data obtained indicate that as carbohydrate consumption increases, the methylation level of the Klotho gene also rises.

References

  • Aczel D, Torma F, Jokai M, McGreevy K, Boros A, Seki Y et al. The circulating level of Klotho is not dependent upon physical fitness and age-associated methylation increases at the promoter region of the Klotho gene. Genes (Basel). 2023;14:525.
  • McLachlan KJJ, Cole JH, Harris SE, Marioni RE, Deary IJ, Gale CR. Attitudes to ageing, biomarkers of ageing and mortality: The Lothian Birth Cohort 1936. J Epidemiol Community Health. 2020;74:377-83.
  • Salameh Y, Bejaoui Y, El Hajj N. DNA methylation biomarkers in aging and age-related diseases. Front Genet. 2020;11:480672.
  • Kuro M. Klotho and calciprotein particles as therapeutic targets against accelerated ageing. Clin Sci. 2021;135:1915-27.
  • Fung TY, Iyaswamy A, Sreenivasmurthy SG, Krishnamoorthi S, Guan XJ, Zhu Z et al. Klotho an autophagy stimulator as a potential therapeutic target for Alzheimer’s disease: a review. Biomedicines. 2022;10.3:705.
  • Kuro-o M. The Klotho proteins in health and disease. Nat Rev Nephrol. 2019;15:27-44.
  • Razzaque MS. Is Klotho an essential player? Am J Physiol Renal Physiol. 2009;296:470-6.
  • Wu SE, Chen YJ, Chen WL. Adherence to Mediterranean diet and soluble Klotho level: the value of food synergy in aging. Nutrients. 2022;14:3910.
  • Dhar GA, Saha S, Mitra P, Nag Chaudhuri R. DNA methylation and regulation of gene expression: guardian of our health. Nucleus (India). 2021;64:259-70.
  • Bond DM, Finnegan EJ. Passing the message on: inheritance of epigenetic traits. Trends Plant Sci. 2007;12:211-6.
  • Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88.
  • Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38:23-38.
  • Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev. 2021;69:101348.
  • Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102.30:10604-9.
  • Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015;14:924-32.
  • Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA. 2012;109:10522-7.
  • Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA. 2006;103.5:1412-7.
  • Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39:457-66.
  • Cortessis VK, Thomas DC, Joan Levine A, Breton C V, Mack TM, Siegmund KD et al. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 2012;131:1565-89.
  • Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13:97-109.
  • Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP et al. Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem. 2006;281:6120-3.
  • Guarnotta V, Pizzolanti G, Petrancosta R, Radellini S, Baiamonte C, Giordano C. Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case–control study. J Endocrinol Invest. 2022;45:1247-54.
  • Drew DA, Katz R, Kritchevsky S, Ix JH, Shlipak MG, Newman AB et al. Soluble Klotho and incident hypertension. Clin J Am Soc Nephrol. 2021;16:1502-11.
  • Donate-Correa J, Ferri CM, Martín-Núñez E, Pérez-Delgado N, González-Luis A, Mora-Fernández C et al. Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease. Sci Rep. 2021;11:15877.
  • Buendia-Roldan I, Machuca N, Mejía M, Maldonado M, Pardo A, Selman M. Lower levels of α-Klotho in serum are associated with decreased lung function in individuals with interstitial lung abnormalities. Sci Rep. 2019;9:10801.
  • Corcillo A, Fountoulakis N, Sohal A, Farrow F, Ayis S, Karalliedde J. Low levels of circulating anti-ageing hormone Klotho predict the onset and progression of diabetic retinopathy. Diab Vasc Dis Res. 2020;17:1479164120970901.
  • Paroni G, Panza F, De Cosmo S, Greco A, Seripa D, Mazzoccoli G. Klotho at the edge of Alzheimer’s disease and senile depression. Mol Neurobiol. 2019;56:1908-20.
  • Izquierdo MC, Perez-Gomez MV, Sanchez-Niño MD, Sanz AB, Ruiz-Andres O, Poveda J et al. Klotho, phosphate and inflammation/ageing in chronic kidney disease. Nephrol Dial Transplant. 2012;27:suppl4:iv6-10.
  • Liu P, Wang Y, Yang G, Zhang Q, Meng L, Xin Y et al. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol Res. 2021;165:105420.
  • Orces CH. The association of obesity and the antiaging humoral factor Klotho among adults in the United States. J Am Coll Nutr. 2019;38:683-9.
  • Zhang H, Shi Y, Ma F, Wang L, Hou Y, Zhu, Z. Association of Klotho single nucleotide polymorphisms with cardiovascular diseases: a systematic review and meta-analysis. Int J Clin Exp Med. 2017;10:5721-41.
  • Hikone K, Hasegawa T, Tsuchiya E, Hongo H, Sasaki M, Yamamoto T et al. Histochemical examination on periodontal tissues of Klotho-deficient mice fed with phosphate-insufficient diet. J Histochem Cytochem. 2017;65:207-21.
  • Maekawa R, Seino Y, Ogata H, Murase M, Iida A, Hosokawa K et al. Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice. J Nutr Biochem. 2017;49:71-9.
  • Wilkens MR, Elfers K, Schmicke M, Breves G, Muscher-Banse AS. Dietary nitrogen and calcium modulate CYP27B1 expression in young goats. Domest Anim Endocrinol. 2018;64:70-6.
  • Milovanova SYu, Milovanov YuS, Taranova M V, Dobrosmyslov IA. Effects of keto/amino acids and a low-protein diet on the nutritional status of patients with stages 3B-4 chronic kidney disease. Ter Arkh. 2017;89:30-3.
  • Zapata RC, Singh A, Pezeshki A, Avirineni BS, Patra S, Chelikani PK. Low‐protein diets with fixed carbohydrate content promote hyperphagia and sympathetically mediated increase in energy expenditure. Mol Nutr Food Res. 2019;63:1900088.
  • Shafie A, Rahimi AM, Ahmadi I, Nabavizadeh F, Ranjbaran M, Ashabi G. High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats’ brain: the toxic role of high-fat diet. Nutr Metab (Lond). 2020;17:86.
  • dos Santos MS, Canale D, Bernardo DRD, Shimizu MHM, Seguro AC, Volpini RA et al. The restoration of vitamin D levels slows the progression of renal ischemic injury in rats previously deficient in vitamin D. Front Med (Lausanne). 2021;8:625647.
  • Hu MC, Kuro-o M, Moe OW. Renal and extrarenal actions of Klotho. Semin Nephrol. 2013;33:118-29.
  • Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF et al. Klotho allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet. 2003;72:1154-61.
  • Ogata N, Matsumura Y, Shiraki M, Kawano K, Koshizuka Y, Hosoi T et al. Association of Klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women. Bone. 2002;31:37-42.
  • Sachdeva A, Gouge J, Kontovounisios C, Nikolaou S, Ashworth A, Lim K et al. Klotho and the treatment of human malignancies. Cancers (Basel). 2020;12:1665.
  • Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012;81:640-50.
  • Kulis M, Esteller M. DNA methylation and cancer. In: Epigenetic Alterations in Oncogenesis (Ed J Tost):27-56. London, Elsevier, 2010.
  • Huang Y, Xu Q, Liu M. Dietary carbohydrates and their impact on DNA methylation: Implications for health. Nutr Neurosci. 2015;18:23-30.
  • Agudo-Lopez A, Miguel BG, Fernandez I, Martinez AM, Araki S, Dobashi K et al. Dietary patterns and DNA methylation in aging and longevity: A cross-sectional study. BMC Geriatr. 2016;16:54
There are 46 citations in total.

Details

Primary Language English
Subjects Medical Biochemistry - Carbohydrates, Medical Biochemistry - Lipids
Journal Section Research
Authors

Esra Karataş 0009-0002-0631-0061

Mehmet Gürbilek 0000-0002-6281-8807

Gamze Demirel 0000-0001-6037-378X

Publication Date December 30, 2024
Submission Date September 16, 2024
Acceptance Date November 22, 2024
Published in Issue Year 2024 Volume: 49 Issue: 4

Cite

MLA Karataş, Esra et al. “Relationship Between Klotho Gene Methylation Level and Diet Habit”. Cukurova Medical Journal, vol. 49, no. 4, 2024, pp. 965-73, doi:10.17826/cumj.1551174.