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HLA- and H-2-associated variations of intra- and extracellular magnesium content
J G Henrotte1, M Pla, J Dausset
1Centre National de la Recherche Scientifique, Faculté de Pharmacie, Paris, France.
Abstract:
Erythrocyte and plasma magnesium (EMg, PMg) levels have been shown to be genetically controlled in human and mouse. The possible association of these genetic factors with the major histocompatibility complex (MHC) (HLA and H-2) was investigated. Among unrelated adult male blood donors, HLA-B35 carriers have PMg (P less than 0.01) and EMg (P less than 0.0005) levels lower than those of noncarriers, while HLA-B38 carriers exhibit a significant (P less than 0.05) increase of both PMg and EMg levels when compared to the other individuals. Furthermore, HLA identical sibs have EMg values more similar than those of HLA different sibs. In the mouse, erythrocyte (P less than 0.001), plasma (P less than 0.001), liver (P less than 0.03), and spleen (P less than 0.04) Mg contents vary significantly according to H-2, with higher values being found in H-2k than in H-2q or H-2b congenic strains. However, non-MHC genes also have an influence on erythrocyte (P less than 10(-10], plasma (P less than 10(-10], spleen (P less than 10(-5], and kidney (P less than 10(-6] Mg contents as shown by differences between H-2 identical strains, which differ by the C3H and B10 genetic backgrounds. In conclusion, genetic factors controlling intra- and extracellular Mg levels are composed of at least three components: MHC (HLA and H-2)-associated genes, non-MHC genes, and tissue factors modulating the respective importance of the first two sets of factors. The mechanisms underlying this genetic system are discussed.
Insights
Genetic factors influence erythrocyte and plasma magnesium (Mg) levels, with associations found with the major histocompatibility complex (MHC) in humans and mice. Non-MHC genes and tissue factors also play a role in regulating Mg concentrations.
Area of Science:
- Genetics
- Immunogenetics
- Biochemistry
Background:
- Erythrocyte and plasma magnesium (EMg, PMg) levels are genetically controlled in humans and mice.
- The major histocompatibility complex (MHC), including human leukocyte antigen (HLA) and mouse H-2, is a key genetic region influencing immune responses.
- Understanding the genetic basis of Mg homeostasis is crucial for metabolic and immunological research.
Purpose of the Study:
- To investigate the association between genetic factors, specifically the MHC, and erythrocyte and plasma magnesium levels in humans and mice.
- To identify specific MHC alleles (HLA and H-2) linked to variations in Mg concentrations.
- To explore the interplay of MHC-associated genes, non-MHC genes, and tissue-specific factors in regulating magnesium homeostasis.
Main Methods:
- Human study: Analyzed Mg levels (EMg, PMg) in unrelated adult male blood donors and HLA-identical siblings, correlating them with specific HLA-B alleles (B35, B38).
- Mouse study: Compared Mg content (erythrocyte, plasma, liver, spleen, kidney) across different H-2 congenic strains and H-2 identical strains with varying genetic backgrounds.
- Statistical analysis was employed to determine the significance of observed differences in Mg levels related to MHC and non-MHC genotypes.
Main Results:
- In humans, HLA-B35 carriers showed lower PMg and EMg, while HLA-B38 carriers exhibited higher levels. HLA-identical siblings had more similar EMg values than HLA-different siblings.
- In mice, H-2 congenic strains displayed significant variations in erythrocyte, plasma, liver, and spleen Mg content, with H-2k strains generally having higher levels.
- Non-MHC genes significantly influenced Mg levels in erythrocytes, plasma, spleen, and kidneys, as evidenced by differences between H-2 identical strains with distinct genetic backgrounds.
Conclusions:
- Genetic factors controlling intra- and extracellular magnesium levels involve at least three components: MHC-associated genes, non-MHC genes, and tissue-specific factors.
- The MHC plays a significant role in regulating magnesium levels, but its influence is modulated by other genetic and tissue-specific elements.
- These findings highlight a complex genetic system governing magnesium homeostasis with implications for understanding metabolic and immune-related disorders.