title: Association of Transcobalamin II (TCN2) and Transcobalamin II-Receptor (TCblR) Genetic Variations With Cobalamin Deficiency Parameters in Elderly Women.
abstract: Cobalamin (vitamin B12) deficiency is a subtle progressive clinical disorder, affecting nearly 1 in 5 individuals > 60 years old. This deficiency is produced by age-related decreases in nutrient absorption, medications that interfere with vitamin B12 absorption, and other comorbidities. Clinical heterogeneity confounds symptom detection for elderly adults, as deficiency sequelae range from mild fatigue and weakness to debilitating megaloblastic anemia and permanent neuropathic injury. A better understanding of genetic factors that contribute to cobalamin deficiency in the elderly would allow for targeted nursing care and preventive interventions. We tested for associations of common variants in genes involved in cobalamin transport and homeostasis with metabolic indicators of cobalamin deficiency (homocysteine and methylmalonic acid) as well as hematologic, neurologic, and functional performance features of cobalamin deficiency in 789 participants of the Women's Health and Aging Studies. Although not significant when corrected for multiple testing, eight single nucleotide polymorphisms (SNPs) in two genes, transcobalamin II (TCN2) and the transcobalamin II-receptor (TCblR), were found to influence several clinical traits of cobalamin deficiency. The three most significant findings were the identified associations involving missense coding SNPs, namely, TCblR G220R (rs2336573) with serum cobalamin, TCN2 S348F (rs9621049) with homocysteine, and TCN2 P259R (rs1801198) with red blood cell mean corpuscular volume. These SNPs may modify the phenotype in older adults who are more likely to develop symptoms of vitamin B12 malabsorption.
authors: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA University of Utah, College of Nursing, Salt Lake City, UT, USA.
authors: Emma L
authors: EL
authors: Kurnat-Thoma
authors: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Faith
authors: F
authors: Pangilinan
authors: Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors: Amy M
authors: AM
authors: Matteini
authors: University of Utah, College of Nursing, Salt Lake City, UT, USA.
authors: Bob
authors: B
authors: Wong
authors: University of Utah, College of Nursing, Salt Lake City, UT, USA.
authors: Ginette A
authors: GA
authors: Pepper
authors: University of Colorado, School of Medicine, Division of Hematology, Denver, CO, USA.
authors: Sally P
authors: SP
authors: Stabler
authors: University of Maryland, School of Medicine, Baltimore, MD, USA.
authors: Jack M
authors: JM
authors: Guralnik
authors: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA lbrody@mail.nih.gov.
authors: Lawrence C
authors: LC
authors: Brody
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D014155:Transcobalamins / Q000235:genetics*; D014806:Vitamin B 12 Deficiency / Q000235:genetics*; D016387:Women's Health
chemical_list: D011956:Receptors, Cell Surface; D014155:Transcobalamins; C028176:transcobalamin receptor
keywords: cobalamin; genetic association; older adults; pernicious anemia; transcobalamin; vitamin B12 deficiency