TAILIEUCHUNG - Báo cáo khoa học: Functional and genetic characterization of the promoter region of apolipoprotein H (b2-glycoprotein I)

This study characterized the human apolipoprotein H [APOH; b2-glycopro-tein I (b2GPI)] promoter and its variants byin vitro functional experiments and investigated their relationship with human plasmab2GPI levels. We examined the individual effects of 12 APOHpromoter single nucleotide polymorphisms in the 5¢ flanking region ofAPOH( kb) on luciferase activity in COS-1 cells and HepG2 cells and their impact on plasma. | ỊFEBS Journal Functional and genetic characterization of the promoter region of apolipoprotein H b2-glycoprotein I Sangita Suresh1 F. Yesim Demirci1 Iliya Lefterov2 Candace M. Kammerer1 Rosalind Ramsey-Goldman3 Susan Manzi4 and M. Ilyas Kamboh1 1 Department of Human Genetics Graduate Schoolof Public Health University of Pittsburgh Pittsburgh PA USA 2 Department of Environmentaland OccupationalHealth Graduate Schoolof Public Health University of Pittsburgh Pittsburgh PA USA 3 Northwestern University Feinberg Schoolof Medicine Division of Rheumatology Chicago IL USA 4 Division of Rheumatology and ClinicalImmunology Lupus Center of Excellence University of Pittsburgh Pittsburgh PA USA Keywords APOH association polymorphisms promoter b2-glycoprotein I Correspondence M. I. Kamboh Department of Human Genetics Graduate School of Public Health Pittsburgh PA 15261 USA Fax 1 412 383 7844 Tel 1 412 624 3066 E-mail kamboh@ Received 2 September 2009 revised 1 December 2009 accepted 7 December 2009 doi This study characterized the human apolipoprotein H APOH p2-glycopro-tein I P2GPI promoter and its variants by in vitro functional experiments and investigated their relationship with human plasma b2GPI levels. We examined the individual effects of 12 APOH promoter single nucleotide polymorphisms in the 5 flanking region of APOH kb on luciferase activity in COS-1 cells and HepG2 cells and their impact on plasma P2GPI levels in 799 American White people the DNA binding properties of the APOH promoter using an electrophoretic mobility shift assay in HepG2 cells the effects of serial deletion analysis of the APOH 5 flanking region in COS-1 and HepG2 cells and cross-species conservation of the APOH promoter sequence. The variant alleles of three single nucleotide polymorphisms -1219G A -643T C and -32C A showed significantly lower luciferase expression 51 40 and 37 respectively as compared with the wild-type allele. The electrophoretic .

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