An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis

Abstract

Background

Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 –75G/A promoter polymorphism has been associated with elevated ApoA1 levels.

Objective

We sought to investigate the effect of the APOA1 –75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS).

Methods

A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao’s Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1.

Results

APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11–0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively).

Conclusions

We found an association of the APOA1 –75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.

Keywords

APOA1 cognitive impairment multiple sclerosis stroop verbal fluency

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References

1 Rao SM Leo GJ Bernardin L Unverzagt F . Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41: 685–691.

2 Bobholz JA Rao SM . Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol 2003; 16: 283–288.

3 Huijbregts SC Kalkers NF de Sonneville LM de Groot V Reuling IE Polman CH . Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS. Neurology 2004; 63: 335–339.

4 Achiron A Barak Y . Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry 2003; 74: 443–446.

5 Kujala P Portin R Ruutiainen J . The progress of cognitive decline in multiple sclerosis. A controlled 3-year follow-up study. Brain 1997; 120: 289–297.

6 Oliveri RL Cittadella R Sibilia G . APOE and risk of cognitive impairment in multiple sclerosis. Acta Neurol Scand. 1999; 100: 290–295.

7 Koutsis G Panas M Giogkaraki E . APOE ε4 is associated with impaired verbal learning in patients with MS. Neurology 2007; 68: 546–549.

8 Shi J Zhao C Vollmer TL Tyry TM Kuniyoshi SM . APOE ε4 is associated with cognitive impairment in patients with multiple sclerosis. Neurology 2008; 70: 185–190.

9 Parmenter BA Denney DR Lynch SG Middleton LS Harlan LM . Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms. Mult Scler 2007; 13: 25–32.

10.

10 Saczynski JS White L Peila RL Rodriguez BL Launer LJ . The relation between apolipoprotein A-I and dementia. The Honolulu-Asia aging study. Am J Epidemiol 2007; 165: 985–992.

11.

11 Merched A Xia Y Visvikis S Serot JM Siest G . Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer’s disease. Neurobiol Aging 2000; 21: 27–30.

12.

12 Kuriyama M Takahashi K Yamano T . Low levels of serum apolipoprotein AI and AII in senile dementia. Jpn J Psychiatry Neurol 1994; 48: 589–593.

13.

13 Groenendijk M Cantor RM de Bruin TWA Dallinga-Thie GM . The apoAI-CIII-AIV gene cluster. Atherosclerosis 2001; 157: 1–11.

14.

14 Polman CH Reingold SC Edan G . Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005; 58: 840–846.

15.

15 Kurtzke JF . Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–1452.

16.

16 Boringa JB Lazeron RH Reuling IE . The brief repeatable battery of neuropsychological tests: normative values allow application in multiple sclerosis clinical practice. Mult Scler 2001; 7: 263–267.

17.

17 Stroop JR . Studies of interference in serial verbal reactions. J Exp Psychol 1935; 18: 643–662.

18.

18 Amato MP Portacccio E Goretti B . The Rao’s brief repeatable battery and Stroop test: normative values with age, education and gender corrections in an Italian population. Mult Scler 2006; 12: 787–793.

19.

19 Beck AT Ward CH Mendelson M Mock J Erbaugh J . An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–571.

20.

20 Dallinga-Thie GM Bu XD van Linde-Sibenius Trip M Rotter JI Lusis AJ de Bruin TW . Apolipoprotein A-I/C-III/A-IV gene cluster in familial combined hyperlipidemia: effects on LDL-cholesterol and apolipoproteins B and C-III. J Lipid Res 1996; 37: 136–147.

21.

21 Amato MP Zipoli V Goretti B . Benign multiple sclerosis. Cognitive, psychological and social aspects in a clinical cohort. J Neurol 2006; 253: 1054–1059.

22.

22 Harr SD Uint L Hollister R Hyman BT Mendez AJ . Brain expression of apolipoproteins E, J and A-I in Alzheimer’s disease. J Neurochem 1996; 66: 2429–2435.

23.

23 Winiewski T Golabek AA Kida E Wisniewski KE Frangione B . Comformational mimicry in Alzheimer’s disease. Role of apolipoproteins in amyloidogenesis. Am J Pathol 1995; 147: 238–244.

24.

24 Remaley AT Stonik JA Demosky SJ . Apolipoprotein specificity for lipid efflux by the human ABCA1 transporter. Biochim Biophys Res Commun 2001; 280: 818–823.

25.

25 Vollbach H Heun R Morris CM . APOA1 promoter polymorphism influences risk of early-onset nonfamiliar AD. Ann Neurol 2005; 58: 436–441.

26.

26 Boyles JK Zoellner CD Anderson LJ . A role for apolipoprotein E, apolipoprotein A-I and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J Clin Invest 1989; 83: 1015–1031.

27.

27 Gelman BB Goodrum J Bouldin TW . Macrophage apolipoprotein synthesis and endoneurial distribution as a result of segmental demeyelination. J Neuropathol Exper Neurol 1991; 50: 383–407.

28.

28 Jurado MB Rosselli M . The elusive nature of executive functions: a review of our current understanding. Neuropsychol Rev 2007; 17: 213–233.

29.

29 Desmond DW . The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit. J Neurol Sci 2004; 226: 3–7.

30.

30 Looi JCL Sachdev PS . Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999; 53: 670–678.

31.

31 Schultz JR Verstuyft JG Gong EL Nichols AV Rubin EM . Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature 1993; 365: 762–764.

32.

32 Luc G Bard JM Ferrieres J . : on behalf of the PRIME Study Group. Value of HDL cholesterol, apolipoprotein A-I, lipoprotein A-I and lipoprotein A-I/A-II in prediction of coronary heart disease: the PRIME study. Arterioscler Thromb Vasc Biol 2002; 22: 1155–1161.