A complete genomic analysis of the apolipoprotein E gene in Chinese patients with lipoprotein glomerulopathy.

Mutations of the apolipoprotein E (apo E) gene are thought to play an etiological role in lipoprotein glomerulopathy (LPG), a novel kidney disease. Evidence suggesting that mutated forms of apo E may be present in LPG includes elevated plasma concentrations of apo E in LPG patients and deposition of apo E in their glomerular capillaries, and there are published reports indicating that mutations of the apo E gene are present in the Japanese LPG patient population. Conflicting reports, however, exist in the current literature. Therefore, to strengthen the theory that apo E gene mutations may be present in LPG pathogenesis, we chose to examine the 5.5 kb genomic DNA encompassing the entire apo E locus and adjoining flanking regions, in 17 Chinese LPG patients and 10 normal controls. Results suggest that there are no apo E gene mutations present in our LPG patients, including previously reported apo E mutations associated with LPG. Surprisingly, however, when the apo E sequence used in the current study was compared against the apo E gene sequence published in GenBank, 10 ethnic variation sites were identified in the noncoding regions. We therefore conclude that apo E gene mutations may not be the only etiology of LPG, and it is likely that other abnormalities could play a role in the pathogenesis of the disease.