The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

doi:10.1186/s12902-022-01097-1

. 2022 Jul 17;22(1):182.

doi: 10.1186/s12902-022-01097-1.

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

Eleanor M Cave¹, Sureka Bhola^{1

2}, Nigel J Crowther^{1

2}, Carolyn J Padoa^{3

4}

Affiliations

¹ Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa.
³ Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. carolyn.padoa@nhls.ac.za.
⁴ Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa. carolyn.padoa@nhls.ac.za.

PMID: 35843941
PMCID: PMC9290305
DOI: 10.1186/s12902-022-01097-1

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

Eleanor M Cave et al. BMC Endocr Disord. 2022.

. 2022 Jul 17;22(1):182.

doi: 10.1186/s12902-022-01097-1.

Authors

Eleanor M Cave¹, Sureka Bhola^{1

2}, Nigel J Crowther^{1

2}, Carolyn J Padoa^{3

4}

Affiliations

¹ Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa.
³ Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. carolyn.padoa@nhls.ac.za.
⁴ Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa. carolyn.padoa@nhls.ac.za.

PMID: 35843941
PMCID: PMC9290305
DOI: 10.1186/s12902-022-01097-1

Abstract

Background: Vitamin D deficiency and the vitamin D pathway have previously been associated with type 1 diabetes (T1D). The majority of vitamin D is transported through the blood bound to the vitamin D binding protein (VDBP). Two polymorphisms in the VDBP gene (rs4588 and rs7041) result in different VDBP variants and have been associated with T1D, however the results are not consistent. The association of VDBP levels and its polymorphisms with T1D have not been investigated in the black South African population. Therefore, this study aimed to determine whether rs4588, rs7041 or serum VDBP levels were associated with T1D in this population.

Methods: Participants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Participants were genotyped for rs4588 and rs7041 using PCR-RFLP and serum VDBP levels were determined by ELISA.

Results: There was no difference in VDBP allelic or genotypic frequencies between participants with T1D and controls (rs4588 C allele frequency 0.92 vs. 0.94; p = 0.390 and rs7041 T allele frequency 0.95 vs. 0.95; p = 0.890). In univariate analysis, the rs4588 CC genotype was associated with increased serum VDBP levels, however, this association was lost with multivariate analysis. The VDBP genotypes were not associated with any other study variables. In logistic regression analysis, higher VBDP levels were associated with T1D (OR: (95% CI): 6.58 (1.45-29.9); p = 0.015), and within a linear regression analysis, T1D disease status was found to be associated with 0.044 mg/ml higher VDBP levels (p = 0.028).

Conclusions: These data suggest that serum VDBP levels are positively associated with the presence of T1D in the African population. Whether VDBP lies in the causal pathway or its elevation is an effect of T1D is uncertain and requires further investigation.

Keywords: Black South African; Type 1 diabetes; Vitamin D binding protein.

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Conflict of interest statement

The authors declare no conflict of interest.

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References

1. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93(6):512–517. doi: 10.1136/adc.2007.128579. - DOI - PubMed
1. Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985;61(5):969–975. doi: 10.1210/jcem-61-5-969. - DOI - PubMed
1. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–959. doi: 10.1210/jcem-63-4-954. - DOI - PubMed
1. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96(4):507–515. - PubMed
1. Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3) Proc Natl Acad Sci U S A. 2001;98(24):13895–13900. doi: 10.1073/pnas.241516998. - DOI - PMC - PubMed

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[1] Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93(6):512–517. doi: 10.1136/adc.2007.128579. - DOI - PubMed

[2] Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93(6):512–517. doi: 10.1136/adc.2007.128579. - DOI - PubMed

[3] Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985;61(5):969–975. doi: 10.1210/jcem-61-5-969. - DOI - PubMed

[4] Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985;61(5):969–975. doi: 10.1210/jcem-61-5-969. - DOI - PubMed

[5] Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–959. doi: 10.1210/jcem-63-4-954. - DOI - PubMed

[6] Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–959. doi: 10.1210/jcem-63-4-954. - DOI - PubMed

[7] Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96(4):507–515. - PubMed

[8] Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96(4):507–515. - PubMed

[9] Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3) Proc Natl Acad Sci U S A. 2001;98(24):13895–13900. doi: 10.1073/pnas.241516998. - DOI - PMC - PubMed

[10] Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3) Proc Natl Acad Sci U S A. 2001;98(24):13895–13900. doi: 10.1073/pnas.241516998. - DOI - PMC - PubMed

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The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

Affiliations

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

Authors

Affiliations

Abstract

Conflict of interest statement

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Cited by

References

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Grants and funding

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Medical

Abstract

Conflict of interest statement

Similar articles

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References

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Medical