Characterization of mutants of the vitamin D-binding protein/group-specific component: molecular evolution of GC*1A2 and GC*1A3, common in some Asian populations.

A well defined polymorphism of vitamin D-binding/group-specific component (GC) residues in exon 11. To characterize the molecular basis of GC*1A2 and GC*1A3, common in some Asian populations, we analyzed all coding exons amplified by the polymerase chain reaction. GC*1F was divided into GC*1FC and GC*1FT by a C-T transition in the third nucleotide of the codon (TGC/T) for cysteine283 in exon 8. The sequencing of exons 8 and 11 showed that GC*1A2 and GC*1A3 had occurred on a GC*1FC genetic background. They also shared a substitution of cysteine (TGC) for arginine (CGC) at position 429 in exon 11. GC*1A2 was characterized by having glycine (GGC) instead of serine (AGC) at position 335 in exon 9. GC*1A2 evolved from GC*1FT by three mutational events, i.e. GC*1FT-->GC*1FC-->GC*1A3-->GC*1A2. No evidence was obtained for the existence of the duplicated gene GC*1F.1A2 suggested by isoelectric focusing (IEF) of serum samples. The idea that the characteristic banding pattern of GC*1F.1A2 after IEF results from partial formation of a disulfide bond in the additional cysteine at position 429 is discussed.