The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Data Collection
2.2. Statistical Analysis
2.3. Ethics Statement
3. Results
3.1. Basic Characteristics of the Study Population
3.2. Correlation between Serological Factors and Uric Acid Levels and Gender Effect
3.3. Correlation between Homocystein and Uric Acid Levels and Gender Effect
3.4. Effect of MTHFR C677T Polymorphism
3.5. Biochemical Characteristics of Patients According to Dementia Sub-Classification
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Ioachimescu, A.G.; Brennan, D.M.; Hoar, B.M.; Hazen, S.L.; Hoogwerf, B.J. Serum uric acid is an independent predictor of all-cause mortality in patients at high risk of cardiovascular disease: A preventive cardiology information system (PreCIS) database cohort study. Arthritis Rheum. 2008, 58, 623–630. [Google Scholar] [CrossRef]
- Marwah, R.K. Comorbidities in gouty arthritis. J. Investig. Med. Off. Publ. Am. Fed. Clin. Res. 2011, 59, 1211–1220. [Google Scholar] [CrossRef]
- Trifiro, G.; Morabito, P.; Cavagna, L.; Ferrajolo, C.; Pecchioli, S.; Simonetti, M.; Bianchini, E.; Medea, G.; Cricelli, C.; Caputi, A.P.; et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005–2009: A nationwide population-based study. Ann. Rheum. Dis. 2013, 72, 694–700. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Lozada, L.G.; Nakagawa, T.; Kang, D.H.; Feig, D.I.; Franco, M.; Johnson, R.J.; Herrera-Acosta, J. Hormonal and cytokine effects of uric acid. Curr. Opin. Nephrol. Hypertens. 2006, 15, 30–33. [Google Scholar] [CrossRef]
- Culleton, B.F.; Larson, M.G.; Kannel, W.B.; Levy, D. Serum uric acid and risk for cardiovascular disease and death: The Framingham Heart Study. Ann. Intern. Med. 1999, 131, 7–13. [Google Scholar] [CrossRef]
- Hu, P.; Seeman, T.E.; Harris, T.B.; Reuben, D.B. Is serum uric acid level associated with all-cause mortality in high-functioning older persons: MacArthur studies of successful aging? J. Am. Geriatr. Soc. 2001, 49, 1679–1684. [Google Scholar] [CrossRef] [PubMed]
- Vasquez-Vivar, J.; Santos, A.M.; Junqueira, V.B.; Augusto, O. Peroxynitrite-mediated formation of free radicals in human plasma: EPR detection of ascorbyl, albumin-thiyl and uric acid-derived free radicals. Biochem. J. 1996, 314 Pt 3, 869–876. [Google Scholar] [CrossRef] [Green Version]
- Newland, H. Hyperuricemia in coronary, cerebral and peripheral arterial disease: An explanation. Med. Hypotheses 1975, 1, 152–155. [Google Scholar] [CrossRef]
- Cheng, D.; Du, R.; Wu, X.Y.; Lin, L.; Peng, K.; Ma, L.N.; Xu, Y.; Xu, M.; Chen, Y.H.; Bi, Y.F.; et al. Serum Uric Acid is Associated with the Predicted Risk of Prevalent Cardiovascular Disease in a Community-dwelling Population without Diabetes. Biomed. Environ. Sci. BES 2018, 31, 106–114. [Google Scholar] [CrossRef]
- Petrikova, J.; Janicko, M.; Fedacko, J.; Drazilova, S.; Madarasova Geckova, A.; Marekova, M.; Pella, D.; Jarcuska, P. Serum Uric Acid in Roma and Non-Roma-Its Correlation with Metabolic Syndrome and Other Variables. Int. J. Environ. Res. Public Health 2018, 15, 1412. [Google Scholar] [CrossRef] [Green Version]
- Tseng, W.C.; Chen, Y.T.; Ou, S.M.; Shih, C.J.; Tarng, D.C. U-Shaped Association Between Serum Uric Acid Levels with Cardiovascular and All-Cause Mortality in the Elderly: The Role of Malnourishment. J. Am. Heart Assoc. 2018, 7, e007523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zuo, M.; Nishio, H.; Lee, M.J.; Maejima, K.; Mimura, S.; Sumino, K. The C677T mutation in the methylene tetrahydrofolate reductase gene increases serum uric acid in elderly men. J. Hum. Genet. 2000, 45, 257–262. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis. Jama 2002, 288, 2015–2022. [Google Scholar] [CrossRef] [PubMed]
- Rasouli, M.L.; Nasir, K.; Blumenthal, R.S.; Park, R.; Aziz, D.C.; Budoff, M.J. Plasma homocysteine predicts progression of atherosclerosis. Atherosclerosis 2005, 181, 159–165. [Google Scholar] [CrossRef] [PubMed]
- Maron, B.A.; Loscalzo, J. The treatment of hyperhomocysteinemia. Annu. Rev. Med. 2009, 60, 39–54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abbott, R.D.; Brand, F.N.; Kannel, W.B.; Castelli, W.P. Gout and coronary heart disease: The Framingham Study. J. Clin. Epidemiol. 1988, 41, 237–242. [Google Scholar] [CrossRef]
- Cohen, E.; Levi, A.; Vecht-Lifshitz, S.E.; Goldberg, E.; Garty, M.; Krause, I. Assessment of a possible link between hyperhomocysteinemia and hyperuricemia. J. Investig. Med. Off. Publ. Am. Fed. Clin. Res. 2015, 63, 534–538. [Google Scholar] [CrossRef]
- Kang, S.S.; Wong, P.W.; Susmano, A.; Sora, J.; Norusis, M.; Ruggie, N. Thermolabile methylenetetrahydrofolate reductase: An inherited risk factor for coronary artery disease. Am. J. Hum. Genet. 1991, 48, 536–545. [Google Scholar]
- Tsang, B.L.; Devine, O.J.; Cordero, A.M.; Marchetta, C.M.; Mulinare, J.; Mersereau, P.; Guo, J.; Qi, Y.P.; Berry, R.J.; Rosenthal, J.; et al. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: A systematic review and meta-analysis of trials and observational studies. Am. J. Clin. Nutr. 2015, 101, 1286–1294. [Google Scholar] [CrossRef]
- Levin, B.L.; Varga, E. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. J. Genet. Couns. 2016, 25, 901–911. [Google Scholar] [CrossRef] [Green Version]
- Rai, V. Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations. Asian Pac. J. Cancer Prev. APJCP 2015, 16, 8093–8100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kolz, M.; Johnson, T.; Sanna, S.; Teumer, A.; Vitart, V.; Perola, M.; Mangino, M.; Albrecht, E.; Wallace, C.; Farrall, M.; et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009, 5, e1000504. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wei, W.; Liu, S.Y.; Zeng, F.F.; Ma, L.; Li, K.S.; Wang, B.Y. Meta-analysis of the association of the C677T polymorphism of the methylenetetrahydrofolate reductase gene with hyperuricemia. Ann. Nutr. Metab. 2012, 60, 44–51. [Google Scholar] [CrossRef] [PubMed]
- Moll, S.; Varga, E.A. Homocysteine and MTHFR Mutations. Circulation 2015, 132, e6–e9. [Google Scholar] [CrossRef] [Green Version]
- Quadri, P.; Fragiacomo, C.; Pezzati, R.; Zanda, E.; Forloni, G.; Tettamanti, M.; Lucca, U. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am. J. Clin. Nutr. 2004, 80, 114–122. [Google Scholar] [CrossRef]
- Peng, Q.; Lao, X.; Huang, X.; Qin, X.; Li, S.; Zeng, Z. The MTHFR C677T polymorphism contributes to increased risk of Alzheimer’s disease: Evidence based on 40 case-control studies. Neurosci. Lett. 2015, 586, 36–42. [Google Scholar] [CrossRef]
- Kang, Y.; Na, D.L.; Hahn, S. A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J. Korean Neurol. Assoc. 1997, 15, 300–308. [Google Scholar]
- Morris, J.C. The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 1993, 43, 2412–2414. [Google Scholar] [CrossRef]
- McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984, 34, 939–983. [Google Scholar] [CrossRef] [Green Version]
- Erkinjuntti, T. Clinical criteria for vascular dementia: The NINDS-AIREN criteria. Dement. Geriatr. Cogn. Disord. 1994, 5, 189–192. [Google Scholar] [CrossRef]
- Petersen, R.C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 2004, 256, 183–194. [Google Scholar] [CrossRef] [PubMed]
- McKeith, I.G.; Boeve, B.F.; DIckson, D.W.; Halliday, G.; Taylor, J.P.; Weintraub, D.; Aarsland, D.; Galvin, J.; Attems, J.; Ballard, C.G. Diagnosis and management of dementia with Lewy bodies. Neurology 2017, 89, 88–100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duskin-Bitan, H.; Cohen, E.; Goldberg, E.; Shochat, T.; Levi, A.; Garty, M.; Krause, I. The degree of asymptomatic hyperuricemia and the risk of gout. A retrospective analysis of a large cohort. Clin. Rheumatol. 2014, 33, 549–553. [Google Scholar] [CrossRef]
- Carmel, R.; Green, R.; Rosenblatt, D.S.; Watkins, D. Update on cobalamin, folate, and homocysteine. Hematol. Am. Soc. Hematol. Educ. Program 2003, 2003, 62–81. [Google Scholar] [CrossRef] [Green Version]
- Mumford, S.L.; Dasharathy, S.S.; Pollack, A.Z.; Perkins, N.J.; Mattison, D.R.; Cole, S.R.; Wactawski-Wende, J.; Schisterman, E.F. Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: Findings from the BioCycle study. Hum. Reprod. (Oxf. Engl.) 2013, 28, 1853–1862. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andreassi, M.; Botto, N.; Cocci, F.; Battaglia, D.; Antonioli, E.; Masetti, S.; Manfredi, S.; Colombo, M.; Biagini, A.; Clerico, A. Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease. Hum. Genet. 2003, 112, 171–177. [Google Scholar] [CrossRef]
- Kang, S.S.; Wong, P.W.; Cook, H.Y.; Norusis, M.; Messer, J.V. Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease. J. Clin. Investig. 1986, 77, 1482–1486. [Google Scholar] [CrossRef]
- Zeng, Q.; Li, F.; Xiang, T.; Wang, W.; Ma, C.; Yang, C.; Chen, H.; Xiang, H. Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in chinese population. Mol. Nutr. Food Res. 2016, 61, 1600351. [Google Scholar] [CrossRef]
- Nakamura, T.; Saionji, K.; Hiejima, Y.; Hirayama, H.; Tago, K.; Takano, H.; Tajiri, M.; Hayashi, K.; Kawabata, M.; Funamizu, M.; et al. Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. Am. J. Kidney Dis. Off. J. Natl. Kidney Found. 2002, 39, 1032–1039. [Google Scholar] [CrossRef]
- Gardemann, A.; Weidemann, H.; Philipp, M.; Katz, N.; Tillmanns, H.; Hehrlein, F.W.; Haberbosch, W. The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease. Eur. Heart J. 1999, 20, 584–592. [Google Scholar] [CrossRef] [Green Version]
- Frosst, P.; Blom, H.J.; Milos, R.; Goyette, P.; Sheppard, C.A.; Matthews, R.G.; Boers, G.J.; den Heijer, M.; Kluijtmans, L.A.; van den Heuvel, L.P.; et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 1995, 10, 111–113. [Google Scholar] [CrossRef] [PubMed]
- Ueland, P.M.; Hustad, S.; Schneede, J.; Refsum, H.; Vollset, S.E. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol. Sci. 2001, 22, 195–201. [Google Scholar] [CrossRef]
- Ho, P.I.; Collins, S.C.; Dhitavat, S.; Ortiz, D.; Ashline, D.; Rogers, E.; Shea, T.B. Homocysteine potentiates beta-amyloid neurotoxicity: Role of oxidative stress. J. Neurochem. 2001, 78, 249–253. [Google Scholar] [CrossRef] [PubMed]
- Choi, S.T.; Kim, J.S.; Song, J.S. Elevated serum homocysteine levels were not correlated with serum uric acid levels, but with decreased renal function in gouty patients. J. Korean Med. Sci. 2014, 29, 788–792. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayden, M.R.; Tyagi, S.C. Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle. Nutr. Metab. 2004, 1, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- So, A.; Thorens, B. Uric acid transport and disease. J. Clin. Investig. 2010, 120, 1791–1799. [Google Scholar] [CrossRef] [Green Version]
- Verhaaren, B.F.; Vernooij, M.W.; Dehghan, A.; Vrooman, H.A.; De Boer, R.; Hofman, A.; Witteman, J.C.; Niessen, W.J.; Breteler, M.M.; Van Der Lugt, A.J.N. The relation of uric acid to brain atrophy and cognition: The Rotterdam Scan Study. Neuroepidemiology 2013, 41, 29–34. [Google Scholar] [CrossRef]
- Desideri, G.; Gentile, R.; Antonosante, A.; Benedetti, E.; Grassi, D.; Cristiano, L.; Manocchio, A.; Selli, S.; Ippoliti, R.; Ferri, C. Uric acid amplifies Aβ amyloid effects involved in the cognitive dysfunction/dementia: Evidences from an experimental model in vitro. J. Cell. Physiol. 2017, 232, 1069–1078. [Google Scholar] [CrossRef]
- Parfenov, V.A.; Ostroumova, O.D.; Ostroumova, T.M.; Kochetkov, A.I.; Fateeva, V.V.; Khacheva, K.K.; Khakimova, G.R.; Epstein, O.I. Vascular cognitive impairment: Pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments. Neuropsychiatr. Dis. Treat. 2019, 15, 1381. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Lin, L.; Zhao, C. Related factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia. Clin. Exp. Hypertens. (N. Y. 1993) 2016, 38, 312–316. [Google Scholar] [CrossRef]
- Bottiglieri, T.; Parnetti, L.; Arning, E.; Ortiz, T.; Amici, S.; Lanari, A.; Gallai, V. Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: A study in an Italian population with dementia. Mech. Ageing Dev. 2001, 122, 2013–2023. [Google Scholar] [CrossRef]
- Tana, C.; Ticinesi, A.; Prati, B.; Nouvenne, A.; Meschi, T. Uric Acid and Cognitive Function in Older Individuals. Nutrients 2018, 10, 975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, F.; Chen, B.; Chen, C.; Huang, J.; Chen, S.; Guo, F.; Hu, Z. Elevated homocysteine levels contribute to larger hematoma volume in patients with intracerebral hemorrhage. J. Stroke Cerebrovasc. Dis. Off. J. Natl. Stroke Assoc. 2015, 24, 784–788. [Google Scholar] [CrossRef] [PubMed]
- Jack, C.R., Jr.; Knopman, D.S.; Jagust, W.J.; Petersen, R.C.; Weiner, M.W.; Aisen, P.S.; Shaw, L.M.; Vemuri, P.; Wiste, H.J.; Weigand, S.D.; et al. Tracking pathophysiological processes in Alzheimer’s disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013, 12, 207–216. [Google Scholar] [CrossRef] [Green Version]
- Walker, L.; McAleese, K.E.; Thomas, A.J.; Johnson, M.; Martin-Ruiz, C.; Parker, C.; Colloby, S.J.; Jellinger, K.; Attems, J. Neuropathologically mixed Alzheimer’s and Lewy body disease: Burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathol. 2015, 129, 729–748. [Google Scholar] [CrossRef]
- Kapasi, A.; DeCarli, C.; Schneider, J.A. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol. 2017, 134, 171–186. [Google Scholar] [CrossRef]
- George, R.L.; Keenan, R.T. Genetics of hyperuricemia and gout: Implications for the present and future. Curr. Rheumatol. Rep. 2013, 15, 309. [Google Scholar] [CrossRef]
- Golbahar, J.; Aminzadeh, M.A.; Al-Shboul, Q.M.; Kassab, S.; Rezaian, G.R. Association of methylenetetrahydrofolate reductase (C677T) polymorphism with hyperuricemia. Nutr. Metab. Cardiovasc. Dis. NMCD 2007, 17, 462–467. [Google Scholar] [CrossRef]
- Itou, S.; Goto, Y.; Suzuki, K.; Kawai, S.; Naito, M.; Ito, Y.; Hamajima, N. Significant association between methylenetetrahydrofolate reductase 677T allele and hyperuricemia among adult Japanese subjects. Nutr. Res. (N. Y.) 2009, 29, 710–715. [Google Scholar] [CrossRef]
- Hong, Y.S.; Lee, M.J.; Kim, K.H.; Lee, S.H.; Lee, Y.H.; Kim, B.G.; Jeong, B.; Yoon, H.R.; Nishio, H.; Kim, J.Y. The C677 mutation in methylene tetrahydrofolate reductase gene: Correlation with uric acid and cardiovascular risk factors in elderly Korean men. J. Korean Med. Sci. 2004, 19, 209–213. [Google Scholar] [CrossRef] [Green Version]
- Lwin, H.; Yokoyama, T.; Yoshiike, N.; Saito, K.; Yamamoto, A.; Date, C.; Tanaka, H. Polymorphism of methylenetetrahydrofolate reductase gene (C677T MTHFR) is not a confounding factor of the relationship between serum uric acid level and the prevalence of hypertension in Japanese men. Circ. J. Off. J. Jpn. Circ. Soc. 2006, 70, 83–87. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hinohara, Y.; Naito, M.; Okada, R.; Yin, G.; Higashibata, T.; Tamura, T.; Kawai, S.; Morita, E.; Wakai, K.; Matsuo, H.; et al. No association between MTHFR C677T and serum uric acid levels among Japanese with ABCG2 126QQ and SLC22A12 258WW. Nagoya J. Med. Sci. 2013, 75, 93–100. [Google Scholar] [PubMed]
Female, n = 597 | Male, n = 264 | p-Value | |
---|---|---|---|
Age (years) | 75.3 ± 10.3 | 73.2 ± 11.3 | 0.008 * |
BMI (kg/m2) | 23.4 ± 3.4 | 23.5 ± 3.0 | 0.740 |
SBP (mmHg) | 129.1 ± 19.1 | 127.4 ± 18.6 | 0.225 |
DBP (mmHg) | 74.6 ± 11.3 | 75.0 ± 11.6 | 0.667 |
Hypertension (%) | 53.4 | 51.5 | 0.603 |
Diabetes (%) | 26.5 | 23.9 | 0.420 |
Smoker (%) | 3.7 | 22.3 | <0.001 * |
Alcohol (%) | 13.6 | 41.7 | <0.001 * |
Dyslipidemia (%) | 8.4 | 6.1 | 0.239 |
CVD (%) | 5.7 | 11.4 | 0.003 * |
Cholesterol, mean ± standard deviation (SD) (mg/dL) | 199.5 ± 38.9 | 184.9 ± 38.0 | <0.0001 * |
Glucose, mean ± SD (mg/dL) | 111.1 ± 37.6 | 110.3 ± 32.1 | 0.685 |
Creatinine, mean ± SD (mg/dL) | 0.8 ± 0.3 | 1.0 ± 0.2 | <0.001 * |
Triglyderide, mean ± SD (mg/dL) | 130.6 ± 69.3 | 127.3 ± 75.4 | 0.090 |
HDL, mean ± SD (mg/dL) | 51.6 ± 13.2 | 46.8 ± 11.8 | <0.001 * |
LDL, mean ± SD (mg/dL) | 114.5 ± 32.4 | 108.0 ± 32.1 | 0.008 |
HbA1c, mean (SD) (%) | 6.0 ± 1.0 | 6.0 ± 1.2 | 0.112 |
VitaminB12, mean (SD) (pmol/L) | 727.0 ± 386.2 | 616.4 ± 299.0 | <0.0001 * |
Folic acid, mean (SD) (nmol/L) | 10.5 ± 4.7 | 9.0 ± 4.4 | <0.0001 * |
Homocysteine, mean (SD) (μmol/L) | 12.4 ± 7.8 | 16.0 ± 11.9 | <0.0001 * |
Uric acid, mean (SD) (mg/dL) | 4.6 ± 1.3 | 5.7 ± 1.4 | <0.0001 * |
MTHFR (C677T) | |||
CC (%) | 32.7 | 33.0 | 0.933 |
CT (%) | 49.6 | 50.4 | 0.829 |
TT (%) | 17.8 | 16.7 | 0.698 |
Female | Male | |||
---|---|---|---|---|
r | p-Value | r | p-Value | |
Age (years) | 0.143 | <0.001 * | 0.008 | 0.903 |
Cholesterol (mg/dL) | −0.003 | 0.943 | 0.037 | 0.558 |
Glucose (mg/dL) | 0.043 | 0.302 | −0.161 | 0.01 * |
Creatinine (mg/dL) | 0.375 | <0.001 * | 0.408 | <0.001 * |
Triglyceride (mg/dL) | 0.219 | <0.001 | 0.084 | 0.201 |
HDL (mg/dL) | −0.180 | <0.001 | −0.023 | 0.729 |
LDL (mg/dL) | 0.009 | 0.829 | 0.024 | 0.718 |
HbA1c (%) | 0.090 | 0.038 * | −0.216 | 0.001 * |
VitaminB12 (pmol/L) | 0.032 | 0.434 | −0.078 | 0.205 |
Folic acid (nmol/L) | 0.013 | 0.758 | 0.020 | 0.753 |
Homocysteine (μmol/L) | 0.174 | <0.001 * | 0.148 | 0.016 * |
Homocysteine > 15 μmol/L, n = 264 (30.7%) | Homocysteine ≤ 15 μmol/L, n = 597 (69.3%) | p-Value | |
---|---|---|---|
Vitamin B12, mean ± SD (pmol/L) | 559.2 ± 352.8 | 742.0 ± 357.2 | <0.001 * |
Folic acid, mean ± SD (nmol/L) | 7.3 ± 3.6 | 11.0 ± 4.6 | <0.001 * |
Uric acid, mean ± SD (mg/dL) | 5.5 ± 1.6 | 4.8 ± 1.3 | <0.001 * |
MTHFR (C677T) | |||
CC (%) | 28.7 | 34.2 | 0.126 |
CT (%) | 50.9 | 49.4 | 0.712 |
TT (%) | 20.4 | 16.3 | 0.159 |
Female | Male | |||
---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
Model 1 | 2.0 (1.4–3.1) | 0.001 | 2.7 (1.4–5.4) | 0.003 * |
Model 2 | 1.0 (1.0–1.1) | 0.022 | 1.0 (0.97–1.0) | 0.014 * |
Model 3 | 1.1 (1.0–1.1) | 0.020 | 1.028 (0.99–1.07) | 0.187 |
Female | Male | |||||||
---|---|---|---|---|---|---|---|---|
CC (n = 195) | CT (n = 296) | TT (n = 106) | p-Value | CC (n = 87) | CT (n = 133) | TT (n = 44) | p-Value | |
Age (years) | 74.6 ± 10.6 | 76 ± 9.7 | 74.9 ± 11 | 0.279 | 72.4 ± 11.3 | 73.1 ± 11.7 | 74.8 ± 9.9 | 0.279 |
BMI (kg/m2) | 23.2 ± 3.7 | 23.4 ± 3.4 | 23.8 ± 3.1 | 0.348 | 23.8 ± 2.9 | 23.4 ± 3.1 | 23.1 ± 2.8 | 0.348 |
Cholesterol (mg/dL) | 202.3 ± 41.7 | 199.1 ± 36.2 | 195.2 ± 40.5 | 0.328 | 182.1 ± 39.1 | 187.6 ± 37.1 | 182.7 ± 38.4 | 0.328 |
Glucose (mg/dL) | 109.7 ± 29 | 111.1 ± 40.9 | 114.1 ± 42.2 | 0.640 | 115.3 ± 32.1 | 108.5 ± 34.6 | 105.5 ± 22.1 | 0.640 |
Creatinine (mg/dL) | 0.82 ± 0.19 | 0.84 ± 0.31 | 0.82 ± 0.17 | 0.631 | 0.97 ± 0.16 | 1.01 ± 0.2 | 1.01 ± 0.19 | 0.631 |
Triglyderide (mg/dL) | 130.2 ± 77 | 128. 9 ± 59.6 | 135.9 ± 78.7 | 0.685 | 126.7 ± 73.1 | 130.5 ± 81.8 | 118.4 ± 57.5 | 0.685 |
HDL (mg/dL) | 51.3 ± 12.3 | 52.2 ± 14.1 | 50.3 ± 12.2 | 0.435 | 46.2 ± 10.9 | 47.2 ± 12.3 | 46.8 ± 12.5 | 0.435 |
LDL (mg/dL) | 116.4 ± 32.4 | 114.1 ± 31.2 | 112.3 ± 35.7 | 0.593 | 105.2 ± 32.6 | 110.7 ± 32.1 | 105.7 ± 31 | 0.593 |
HbA1c (%) | 6.0 ± 1 | 6 ± 1.1 | 6.1 ± 1.1 | 0.894 | 6.1 ± 1.2 | 5.9 ± 1.2 | 5.9 ± 0.9 | 0.894 |
VitaminB12 (pmol/L), | 727.4 ± 377 | 727.9 ± 420 | 723.6 ± 297 | 0.995 | 609.1 ± 276.3 | 616.4 ± 288.4 | 631 ± 371.9 | 0.995 |
Folic acid (nmol/L) | 11 ± 4.7 | 10.2 ± 4.7 | 10.1 ± 4.6 | 0.130 | 9.6 ± 4.2 | 9.0 ± 4.6 | 7.4 ± 3.8 | 0.130 |
Homocysteine (μmol/L) | 11.5 ± 3.9 | 12.2 ± 4.8 | 14.9 ± 15.6 | 0.001 * | 14.1 ± 5.2 | 14.4 ± 6.5 | 24.2 ± 24.3 | 0.001 * |
Uric acid (mg/dL) | 4.7 ± 1.4 | 4.6 ± 1.3 | 4.7 ± 1.2 | 0.428 | 5.6 ± 1.5 | 5.8 ± 1.3 | 5.7 ± 1.3 | 0.428 |
Dementia Classification | ||||||||
---|---|---|---|---|---|---|---|---|
AD (n = 374) | AD with CVD (n = 65) | VD (n = 94) | MCI (n = 185) | DLB (n = 48) | NPH (n = 36) | Others (n = 69) | p-Value | |
Age (years) | 77.8 ± 9.0 | 81.2 ± 7.5 | 74.3 ± 10.6 | 66.7 ± 10.6 | 80.1 ± 7.3 | 75.8 ± 9.7 | 71.7 ± 7.2 | 0.000 * |
Sex (F %) | 74 | 72 | 51 | 70 | 77 | 61 | 55 | 0.016 * |
BMI (kg/m2) | 23.2 ± 3.7 | 23.4 ± 3.4 | 23.8 ± 3.1 | 23.8 ± 3.1 | 23.8 ± 2.9 | 23.4 ± 3.1 | 23.1 ± 2.8 | 0.348 |
SBP (mmHg) | 129.7 ± 20.2 | 134.6 ± 16.2 | 135.3 ± 20.1 | 124.8 ± 15.5 | 129.3 ± 16.7 | 122.9 ± 21.1 | 122.6 ± 19.8 | 0.027 * |
DBP (mmHg) | 74.6 ± 11.6 | 76.5 ± 13.0 | 79.1 ± 10.1 | 74.5 ± 10.1 | 73.7 ± 11.2 | 71.4 ± 11.1 | 70.4 ± 12.1 | 0.224 |
Hypertension (%) | 25.4 | 76.9 | 67.0 | 38.9 | 64.5 | 44.4 | 39.1 | 0.099 |
Diabetes (%) | 24.5 | 30.7 | 41.4 | 16.2 | 27.0 | 30.5 | 21.7 | 0.666 |
Smoker (%) | 8.37 | 6.15 | 13.8 | 10.2 | 4.16 | 19.4 | 7.24 | 0.285 |
Alcohol (%) | 19.1 | 10.7 | 29.7 | 29.7 | 8.33 | 11.1 | 28.9 | 0.103 |
Dyslipidemia (%) | 8.37 | 3.07 | 6.52 | 11.3 | 2.08 | 5.55 | 7.24 | 0.730 |
CVD (%) | 4.05 | 13.8 | 22.3 | 3.24 | 4.16 | 11.1 | 10.1 | 0.091 |
Cholesterol (mg/dL) | 197.5 ± 39.1 | 179.7 ± 34.1 | 189 ± 41.8 | 195.5 ± 37.3 | 199.3 ± 43.5 | 194.6 ± 32.8 | 195 ± 30.4 | 0.265 |
Glucose (mg/dL) | 111.8 ± 39.1 | 107.5 ± 26.1 | 113.4 ± 36 | 103.8 ± 20 | 114.1 ± 38.2 | 105.6 ± 32.1 | 114.4 ± 22.1 | 0.175 |
Creatinine (mg/dL) | 0.87 ± 0.20 | 0.96 ± 0.33 | 0.95 ± 0.51 | 0.81 ± 0.14 | 0.92 ± 0.23 | 0.86 ± 0.21 | 0.78 ± 0.19 | 0.004 * |
Triglyderide (mg/dL) | 128.9 ± 69.4 | 129.6 ± 68.0 | 139.7 ± 78.4 | 119.8 ± 65.8 | 144.3 ± 89.8 | 140.8 ± 76.3 | 138.1 ± 57.5 | 0.319 |
HDL (mg/dL) | 50.2 ± 12.3 | 47.3 ± 9.95 | 47.9 ± 12.2 | 51.5 ± 13.6 | 49.0 ± 16.1 | 49.3 ± 13.3 | 50.08 ± 12.5 | 0.435 |
LDL (mg/dL) | 113.9 ± 31.8 | 103.4 ± 29.9 | 108.8 ± 33.0 | 112.7 ± 31.8 | 115.3 ± 37.1 | 112.0 ± 26.9 | 112.4 ± 31.0 | 0.643 |
HbA1c (%) | 6.0 ± 1.1 | 6.1± 1.0 | 6.0 ± 1.0 | 5.7 ± 0.7 | 6.0 ± 0.8 | 6.2 ± 1.2 | 5.9 ± 0.9 | 0.322 |
VitaminB12 (pmol/L) | 693.7 ± 369 | 668.2 ± 423 | 701.2 ± 362 | 719.4 ± 315 | 717.7 ± 472 | 675.2 ± 369 | 687.7 ± 371 | 0.930 |
Folic acid (nmol/L) | 9.87 ± 4.7 | 8.60 ± 4.5 | 9.42 ± 4.6 | 11.2 ± 4.5 | 8.61 ± 4.8 | 10.1 ± 5.3 | 9.39 ± 4.0 | 0.006 * |
Homocysteine (μmol/L) | 13.6 ± 8.4 | 19.7 ± 18.2 | 13.8 ± 6.9 | 10.5 ± 5.7 | 15.3 ± 5.7 | 14.4 ± 8.9 | 13.5 ± 3.92 | 0.000 * |
Uric acid (mg/dL) | 4.93 ± 1.4 | 5.20 ± 1.6 | 5.24 ± 1.2 | 4.79 ± 1.2 | 4.79 ± 1.4 | 4.87 ± 1.5 | 4.93 ± 1.5 | 0.206 |
MMSE | 19.0 ± 6.3 | 17.1 ± 5.8 | 19.7 ± 6.6 | 25.3 ± 4.0 | 18.1 ± 5.7 | 18.7 ± 7.3 | 17.7 ± 6.3 | 0.000 * |
CDR | 1.05 ± 0.58 | 1.36 ± 0.63 | 1.13 ± 0.62 | 0.62 ± 0.36 | 1.06 ± 0.54 | 1.24 ± 0.70 | 1.26 ± 0.15 | 0.000 * |
MTHFR | 0.222 | |||||||
CC (%) | 123 (32.9) | 14 (21.7) | 31 (33.0) | 72 (38.9) | 14 (29.1) | 9 (25.0) | 19 (27.5) | |
CT (%) | 197 (52.6) | 34 (52.1) | 47 (50.0) | 74 (40.0) | 27 (56.3) | 17 (47.2) | 33 (47.8) | |
TT (%) | 53 (14.3) | 17 (26.0) | 16 (17.0) | 39 (21.0) | 7 (14.6) | 10 (27.8) | 9 (13.0) |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Kim, H.-J.; Sohn, I.W.; Kim, Y.S.; Jun, J.-B. The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment. Nutrients 2020, 12, 1147. https://doi.org/10.3390/nu12041147
Kim H-J, Sohn IW, Kim YS, Jun J-B. The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment. Nutrients. 2020; 12(4):1147. https://doi.org/10.3390/nu12041147
Chicago/Turabian StyleKim, Hee-Jin, Il Woong Sohn, Young Seo Kim, and Jae-Bum Jun. 2020. "The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment" Nutrients 12, no. 4: 1147. https://doi.org/10.3390/nu12041147