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Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.
Pharmacogenet Genomics. 2012 Oct; 22(10):716-24.PG

Abstract

INTRODUCTION

Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial.

OBJECTIVES

The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A).

METHODS

A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1).

RESULTS

The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 μmol/l) as compared with the controls (14.0±9.6 μmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients.

CONCLUSION

The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Authors+Show Affiliations

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland. monika-bialecka@post.plNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22890010

Citation

Białecka, Monika, et al. "Association of COMT, MTHFR, and SLC19A1(RFC-1) Polymorphisms With Homocysteine Blood Levels and Cognitive Impairment in Parkinson's Disease." Pharmacogenetics and Genomics, vol. 22, no. 10, 2012, pp. 716-24.
Białecka M, Kurzawski M, Roszmann A, et al. Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. Pharmacogenet Genomics. 2012;22(10):716-24.
Białecka, M., Kurzawski, M., Roszmann, A., Robowski, P., Sitek, E. J., Honczarenko, K., Gorzkowska, A., Budrewicz, S., Mak, M., Jarosz, M., Gołąb-Janowska, M., Koziorowska-Gawron, E., Droździk, M., & Sławek, J. (2012). Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. Pharmacogenetics and Genomics, 22(10), 716-24. https://doi.org/10.1097/FPC.0b013e32835693f7
Białecka M, et al. Association of COMT, MTHFR, and SLC19A1(RFC-1) Polymorphisms With Homocysteine Blood Levels and Cognitive Impairment in Parkinson's Disease. Pharmacogenet Genomics. 2012;22(10):716-24. PubMed PMID: 22890010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. AU - Białecka,Monika, AU - Kurzawski,Mateusz, AU - Roszmann,Anna, AU - Robowski,Piotr, AU - Sitek,Emilia J, AU - Honczarenko,Krystyna, AU - Gorzkowska,Agnieszka, AU - Budrewicz,Sławomir, AU - Mak,Monika, AU - Jarosz,Monika, AU - Gołąb-Janowska,Monika, AU - Koziorowska-Gawron,Ewa, AU - Droździk,Marek, AU - Sławek,Jarosław, PY - 2012/8/15/entrez PY - 2012/8/15/pubmed PY - 2013/1/25/medline SP - 716 EP - 24 JF - Pharmacogenetics and genomics JO - Pharmacogenet Genomics VL - 22 IS - 10 N2 - INTRODUCTION: Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. OBJECTIVES: The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). METHODS: A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). RESULTS: The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 μmol/l) as compared with the controls (14.0±9.6 μmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. CONCLUSION: The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations. SN - 1744-6880 UR - https://www.unboundmedicine.com/medline/citation/22890010/Association_of_COMT_MTHFR_and_SLC19A1_RFC_1__polymorphisms_with_homocysteine_blood_levels_and_cognitive_impairment_in_Parkinson's_disease_ L2 - https://doi.org/10.1097/FPC.0b013e32835693f7 DB - PRIME DP - Unbound Medicine ER -