PLASMA HOMOCYSTEINE IN PATIENTS OF MIGRAINE WITHOUT AURA

Authors

  • Faraz Ahmed Bokhari
  • Tania A. Shakoori
  • Syed Ahmad A. Hassan
  • Hamid J. Qureshi
  • Ghulam A. Qureshi

Abstract

Background: Few studies have studied the role of homocysteine in migraineurs and have producedconflicting results. The MTHFR C677T genotype has been associated with increased risk of migrainein selected clinical samples. We assessed the association of the MTHFR C677T variant with migraine,the corresponding homocysteine levels and their correlation. Method: We studied 27 random adultmigraineurs with aura (MWA), migraine without aura (MWOA), and 32 non-migraineurs (controls)from Lahore, Pakistan in this pilot study which is still under progress. Results: We found significantdifferences in homocysteine levels between various diagnostic groups (K-W test: p=0.005). One-wayANOVA, post-hoc tests revealed significant differences in homocysteine levels between Nonmigraineurs, MWA (p=0.002, CI: 1.93 – 9.19) and MWoA (p=0.002, CI: -9.19 – -1.9). We found asignificant association between the migraine group and C677T-MTHFR variant mutant allele (C/T)(p=0.039). We did not find a significant association between C677T-MTHFR variant andhomocysteine levels. Conclusion: In this pilot study, we found plasma homocysteine levels to besignificantly associated with MWOA. Additionally, plasma homocysteine levels were lower in MWAthan in MWOA. Furthermore, we did not find a relationship between homocysteine levels and theMTHFR variant (SNP rs1801133). Lastly, there may be a relationship between the MTHFR variant(SNP rs1801133) and migraine in this population.Keywords: Plasma homocysteine, Migraine

References

Headache Classification Committee of the International

Headache Society. The international Classification of

Headache Disorders, 2nd Edition. Cephalalgia 2004;24(Supp

:1–152.

Montagna P. Molecular genetics of migraine headaches: a

review. Cephalalgia 2000;20:3–14.

Russell M, Iselius L, Olesen J. Inheritance of migraine

investigated by complex segregation analysis. Hum Genet

;96:726–30.

Ducros A, Tournier-Lasserve E, Bousser MG. The genetics

of migraine. Lancet Neurol 2002;1(5):285–93.

De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L,

Morgante L, et al. Haploinsufficiency of ATP1A2 encoding

the Na+/K+ pump alpha2 subunit associated with familial

hemiplegic migraine type 2. Nat Genet 2003;33:192–6.

Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J,

Svensson DA, et al. Genetic and environmental influences on

migraine: a twin study across six countries. Twin Res

;6:422–31.

Edvinsson L, Uddman R: Neurobiology in primary

headaches. Brain Res Brain Res Rev 2005;48:438–56.

Oterino A, Pascual J, Ruiz de Alegria C, Valle N, Castillo J,

Bravo Y, et al. Association of migraine and ESR1 G325C

polymorphism. Neuroreport 2006;17:61–4.

Colson N, Lea R, Quinlan S, MacMillan J, Griffiths L.

Investigation of hormone receptor genes in migraine.

Neurogenetics 2005;6:17–23.

Schlesinger I, Hering R. Homocysteine levels in migraine

patients. Cephalalgia 1997;17:46. [Letter to Editor]

Evers S, Koch HG, Husstedt IW. Plasma homocysteine levels

in primary headache. In: Olesen J, Edvinsson L, editors.

Headache pathogenesis: monoamines, neuropeptides,

purines, and nitric oxide. Philadelphia: Lippincott-Raven

Publishers; 1997.p. 215–8.

Kowa H, Yasui K, Takeshima T, Urakami K, Sakai F,

Nakashima K. The homozygous C677T mutation in the

methylenetetrahydofolate reductase gene is a genetic risk

factor for migraine. Am J Med Genet 2000;96:762–4.

Bianchi A, Salomone S, Caraci F, Pizza V, Bernardini R,

D'Amato CC. Role of magnesium, coenzyme Q10,

riboflavin, and vitamin B12 in migraine prophylaxis. Vitam

Horm 2004;69:297–312.

Tommaso MD, Losito L, Livrea P. The role of homocysteine

in the pathogenesis and development of migraine.

Cephalalgia 2005;25:863–1020.

Doitsini S, Tsirka E, Tsirka V. Migraine, transient ischaemic

attacks; methylenetetrayhydrofolate reductase gene

polymorphism (C677T-MTHFR) associations and questions.

A retrospection in bibliography. Cephalalgia 2005;25:863–

Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA,

Matthews RG, et al. A candidate genetic risk factor for

vascular disease: a common mutation in

methylenetetrahydrofolate reductase. Nat Genet

;10:111–3.

Wald DS, Law M, Morris JK. Homocysteine and

cardiovascular disease: evidence on causality from a metaanalysis. BMJ 2002;325:1202.

Kara I, Sazci A, Ergul E, Kaya G, Kilic G. Association of the

C677T and A1298C polymorphisms in the 5, 10

J Ayub Med Coll Abbottabad 2010;22(2)

http://www.ayubmed.edu.pk/JAMC/PAST/22-2/Faraz.pdf 55

methylenetetrahydrofolate reductase gene in patients with

migraine risk. Brain Res Mol Brain Res 2003;111:84–90.

Lea RA, Ovcaric M, Sundholm J, MacMillan J, Griffiths LR.

The methylenetetrahydrofolate reductase gene variant C677T

influences susceptibility to migraine with aura. BMC Med

;12:2–3.

Scher AI, Terwindt GM, Verschuren WM, Kruit MC, Blom

HJ, Kowa H, et al. Migraine and MTHFR C677T genotype in

a population-based sample. Ann Neurol 2006;59:372–5.

Kaunisto MA, Kallela M, Hämäläinen E, Kilpikari R,

Havanka H, Harno H. et al. Testing of variants of the

MTHFR and ESR1 genes in 1798 Finnish individuals fails to

confirm the association with migraine with aura. Cephalalgia

;26:1462–72.

Oterino A, Valle N, Bravo Y, Munoz P, Sanchez-Velasco P,

Ruiz-Alegria C, et al. MTHFR T677 homozygosis influences

the presence of aura in migraineurs. Cephalalgia

;24:491–4.

Todesco L, Angst C, Litynski P, Loehrer F, Fowler B,

Haefeli WE. Methylenetetrahydrofolate reductase

polymorphism, plasma homocysteine and age. Euro J Clin

Investig 1999;29:1003–9.

Rodriguez-Esparragon F, Hernandez-Perera O, RodriguezPerez JC, Anabitarte A, Diaz-Cremades JM, Losada A, et al.

The effect of methylenetetrahydrofolate reductase C677T

common variant on hypertensive risk is not solely explained

by increased plasma homocysteine values. Clin Exp

Hypertens 2003;25:209–20.

Zhang Y, Ke X, Shen W, Liu Y. Relationship of

homocysteine and gene polymorphisms of its related

metabolic enzymes with Alzheimer’s Disease. Chin Med Sci

J 2005;20:247–51.

da Silva VC, Ramos FJ, Freitas EM, de Brito-Marques PR,

Cavalcanti MN, D'Almeida V. Alzheimer’s disease in

Brazilian elderly has a relation with homocysteine but not

with MTHFR polymorphisms. Arq Neuropsiquiatr

;64:941–5.

Bosco P, Gueant-Rodriguez RM, Anello G, Spada R,

Romano A, Fajardo A, et al. Association of homocysteine

(but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66

A>G and TCN2 776 C>G) with ischaemic cerebrovascular

disease in Sicily. Thromb Haemost 2006;96(2):154–9.

Ducros V, Demuth K, Sauvant MP, Quillard M, Causse E,

Candito M, et al. Methods for homocysteine analysis and

biological relevance of the results. J Chromatogr B Analyt

Technol Biomed Life Sci 2002;781;207–26.

Helms, C. Salting out Procedure for Human DNA extraction.

In The Donis-Keller Lab –Lab Manual Homepage [online].

Rubino E, Ferrero M, Rainero I, Binello E, Vaula G, Pinessi

L. Association of the C677T polymorphism in the MTHFR

gene with migraine: a meta-analysis. Cephalalgia

;29:818–25.

Cronin S, Furie KL, Kelly PJ. Dose-related association of

MTHFR 677T allele with risk of ischemic stroke: evidence

from a cumulative meta-analysis. Stroke 2005;36:1581–7.

Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten

EG. MTHFR 677C–T polymorphism and risk of coronary

heart disease: a meta-analysis. JAMA 2002;288:2023–31.

Muniz MT, Siqueira ER, Fonseca RA, D'Almeida V, Hotta

JK, dos Santos JE, et al. Evaluation of MTHFR C677T Gene

Polymorphism and Homocysteine Level in Coronary

Atherosclerotic Disease. Arq Bras Endocrinol Metab

;50:1059–65.

da Silva VC, Ramos FJC, Freitas EM, de Brito-Marques PB,

Cavalcanti MNH, D’Almeida V, et al. Alzheimer’s disease in

Brazilian elderly has a relation with homocysteine but not

with MTHFR polymorphisms. Arq Neuropsiquiatr

;64:941–5.

Bosco P, Guéant-Rodriguez RM, Anello G, Spada R,

Romano A, Fajardo A, et al. Association of homocysteine

(but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66

A>G and TCN2 776 C>G) with ischaemic cerebrovascular

disease in Sicily. Thromb Haemost 2006;96:154–9.

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Published

2010-06-01

Issue

Vol. 22 No. 2 (2010): JOURNAL OF AYUB MEDICAL COLLEGE, ABBOTTABAD

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ORIGINAL ARTICLE

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