Identification and characterization of polymorphisms at the HSA alpha1-acid glycoprotein (ORM*) gene locus in Caucasians

Abstract

Human α 1 -acid glycoprotein (AGP) or orosomucoid (ORM) is a major acute phase protein that is thought to play a crucial role in maintaining homeostasis. Human AGP is the product of a cluster of at least two adjacent genes located on HSA chromosome 9. Using a range of restriction endonucleases we have investigated DNA variation at the locus encoding the AGP genes in a panel of healthy Caucasians. Polymorphisms were identified using BamHI, EcoRI, BglII, PvuII, HindIII, TaqI and MspI. Non-random associations were found between the BamHI, EcoRI, BglII RFLPs. The RFLPs detected with PvuII, TaqI and MspI were all located in exon 6 of both AGP genes. The duplication of an AGP gene was observed in 11% of the indiviuals studied and was in linkage disequilibrium with the TaqI RFLP. The identification and characterization of these polymorphisms will prove useful for other population and forensic studies.

Inter‐ethnic differences in pharmacokinetics—is there more that unites than divides?

“… 16 Levels of AAG may be affected by a number of environmental factors 17 and there are polymorphisms that show differences in AAG allele frequencies between ethnic groups. 18 , 19 …”

“…Zhou et al, (1990) showed that there was a higher unbound fraction of disopyramide, propranolol, and diphenhydramine in Chinese patients ( n = 8) compared to White patients ( n = 8) and they attributed this to lower levels of AAG in the Chinese 16 . Levels of AAG may be affected by a number of environmental factors 17 and there are polymorphisms that show differences in AAG allele frequencies between ethnic groups 18,19 …”

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

“…Although the variants of this glycoprotein have been previously defined using electrophoretic characteristics (Weidinger et al, 1987;Nevo et al, 1996;Yuasa et al, 1997;Owczarek et al, 2002;Yuasa et al, 2006), the recent application of gene-specific PCR and sequencing methods has provided the possibility to distinguish the genetic heterogeneity of ORM1.…”

“…Although the rearrangement of the ORM1 and ORM2 genes was not specifically evaluated in our population, because it was not the main objective of this study, several interesting results have been recently described. The frequencies of duplicated or triplicate genes encoding ORM1 and ORM2 proteins, together with the appearance of different gene arrangements, may distinguish some populations, in terms of their ORM diversity (Nakamura et al, 2000;Owczarek et al, 2002;Yuasa et al, 2006). For example, the duplication of ORM1 gene is frequent in Africans and Japanese (high as 10-20%) (Nakamura et al, 2000;Yuasa et al, 2006), and other studies dealing with European and Australian populations suggest that the increase in gene numbers may occur at appreciable frequencies (Dente et al, 1987;Rocha et al, 1993;Owczarek et al, 2002).…”

Genetic variations of orosomucoid genes associated with serum alpha‐1‐acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer

“…AGP is highly polymorphic, and more than 70 AGP variations in the serum have been identified by isoelectric focusing methods 8 . ORM genetic variations, mainly focusing on the exon regions, have been investigated in several ethnic populations, and ethnic differences were recognized 9–13. Duplications or null variations of ORM genes have been also detected in several populations, and the frequency of ORM1 duplication in Japanese subjects was reported to be approximately 20%, although null variations of ORM genes were very rare 8,14,15.…”