The gastric intrinsic factor polymorphism, A68G, modifies the association between the transcobalamin polymorphism, C776G, and vitamin B12 status

Abstract

Gastric intrinsic factor (GIF) and transcobalamin (TC) are required for absorption of vitamin B12 across the ileal enterocyte. Polymorphisms in GIF (A68G) and TC (C776G) have been identified. Previously, we observed differences in plasma holoTC and homocysteine levels among individuals with the TC C776G polymorphism in a cohort of elderly Latinos (Sacramento Area Latino Study on Aging ‐ SALSA). Little is known about the effect of GIF A68G on indicators of B12 status, although the polymorphism has been linked to risk of pernicious anemia. In this study we investigated the prevalence of GIF A68G and its association with B12 status and TC genotype in the SALSA cohort (N=813, age 60–93y). The distribution of GIF genotypes was 94% wild‐type (AA) and 6% heterozygotes (AG), with 1 subject homozygous for the variant isoform (GG). No differences among the GIF genotypes were observed in total B12, holoTC, or homocysteine. However, interactions between GIF genotype and TC genotype were observed on total B12 (p=0.007) and holoTC (p=0.05) such that subjects with both the GIF 68G allele and TC 776G allele had lower total B12 and holoTC than all other allelic combinations. There was no interaction between the GIF and TC genotypes on homocysteine. The GIF A68G polymorphism is prevalent in elderly Latinos and combined with the TC C776G polymorphism may influence B12 absorption and status. NIH AG12975; USDA 00–35200–9073