Significance of Blood Cellular lxr-a Gene Aberration in Coronary Heart Disease Subjects

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Significance of Blood Cellular lxr-α Gene Aberration in Coronary Heart Disease Subjects

Author Affiliations

¹Dept. of Experimental Medicine and Biotechnology, P. G. Institute of Medical Education and Research, Chandigarh, INDIA
² Dept. of Cardiology, P. G. Institute of Medical Education and Research, Chandigarh, INDIA

Res. J. Recent Sci., Volume 1, Issue (1), Pages 69-72, January,2 (2012)

Abstract

Keeping in view our previous finding that unambiguously revealed a significant positive correlation between the expression of mutated Liver X Receptor (LXR)- α gene and the extent of coronary heart disease (CHD), the present study was addressed to explore whether or not this observed blood cellular LXR- α gene aberration is pathognomonic feature of CHD. To detect previously reported blood cellular LXR-α gene aberration restriction digestion was performed with TaaI endonuclease in the LXR-α ligand binding domain derived from the cDNA library of peripheral blood mononuclear cells isolated from different unrelated inflammatory disease group (Rheumatic heart disease, Diabetes, Psoriasis and Tuberculosis ) including coronary heart disease. Inheritance of reported blood cellular LXR-α gene aberration was also checked in a family having a higher risk of CHD.Results of our study revealed that LXR-α gene aberration was not only selectively and specifically observed in the blood mononuclear cells derived from CHD patients but also showed a nonmendelian epigenetic inheritance in a family having higher risk of CHD. Based upon these results we propose that blood cellular LXR-α gene aberration may have the potential to act as a noninvasive marker for the early diagnosis of subjects that are at high risk of development of CHD.

References

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Dave V.P., Kaul D., Sharma Y.P., Bhattacharya R., Functional genomics of blood cellular LXR- gene in human coronary heart disease, J. Mol. Cellu. Cardiol., (46), 536–544 (2009)
Boyum A., Ficoll-Hypaque method for separating mononuclear cells and granulaocytes from human blood, Scand. J. Clin. Lab. Invest.,(779), 57–62 (1968)
Chomczynski P. and Sacchi N., Single step method of RNA isolation by acid guanidium thiocynate phenol chloroform extraction, Anal. Biochem.,(162), 156–159 (1987)

[ref1] Marenberg M.E., Risch N., Berkman L.F. et al., Genetic susceptibility to death from coronary heart disease in a study of twins. N. Engl. J. Med.,(330), 1041–1046 (1994)

[ref2] Lusis A.J., Fogelman A.M., Fonarow G.C., Genetic basis of atherosclerosis: part I: new genes and pathways, Circulation, (110), 1868–1873 (2004)

[ref3] Kutuk O. and Basaga H., Inammation meets oxidation: NF-kB as a mediator of initial lesion development in atherosclerosis, Trends. Mol. Med., (9), 549–557 (2003)

[ref4] Ross R., Atherosclerosis: an inammatory disease, N. Engl. J. Med.,(340), 115–126 (1999)

[ref5] Joseph S.B., Castrillo A., Laftte B.A., Mangelsdorf D.J., Tontonoz P., Reciprocal regulation of inammation and lipid metabolism by liver X receptors, Nat. Med.(9), 213–219 (2003)

[ref6] Tontonoz P. and Mangelsdorf D.J., Liver X receptor signaling pathways in cardiovascular disease, Mol. Endocrinol., (17), 985–993 (2003)

[ref7] Dave V.P., Kaul D., Sharma Y.P., Bhattacharya R., Functional genomics of blood cellular LXR- gene in human coronary heart disease, J. Mol. Cellu. Cardiol., (46), 536–544 (2009)

[ref8] Boyum A., Ficoll-Hypaque method for separating mononuclear cells and granulaocytes from human blood, Scand. J. Clin. Lab. Invest.,(779), 57–62 (1968)

[ref9] Chomczynski P. and Sacchi N., Single step method of RNA isolation by acid guanidium thiocynate phenol chloroform extraction, Anal. Biochem.,(162), 156–159 (1987)