Dataset Information

Assessment of rs4588 Allele Impact on 25-OH-D Concentration in Blood of Caucasian Adults

ABSTRACT: Abstract

Objectives

An important point of contention is whether genetic variation has meaningful impact on vitamin D adequacy on top of known modulators like season, fat mass, skin pigmentation and geographic latitude. Answers could come from information generated by numerous published studies. As a first step towards integration of these often diverse data, the impact of the commonly measured single nucleotide variant rs4588 of the GC gene on 25-hydroxy vitamin D (25OHD) concentration in blood of healthy Caucasian adults was assessed with a systematic review and metaanalysis of published findings.

Methods

Selection criteria for inclusion of studies in the analyses were Caucasian healthy adults and listing of average 25OHD concentration in plasma or serum by rs4588 or the tightly linked rs2282679 genotypes. Percent differences between genotypes were extracted from included publications. A random-effects model of metaanalysis was performed using STAT 16.

Results

Of the studies meeting inclusion criteria, published between 2005 and 2019, 35 reported genotype-specific 25OHD concentrations in a total of 59,939 Caucasian adults. The weighted averages were 25.3, 23.2 and 20.4 ng/ml for the GC rs4588 CC, AC and AA genotypes. Relative differences are more informative than absolute concentrations since they are much less affected by calibration discrepancies. The CA carriers had 6.8% lower concentrations than CC carriers and AA carriers 15% lower concentrations when using averages weighted by cohort size. Eight of the included studies with a total number of 15,329 individuals reported standard deviations for the genotype-specific 25OHD concentrations and only these were included for the metaanalysis. The average effect size was −0.44 (95% CI; −0.89, 0.01) for carriers of a single rs4588 A allele, and −0.59 (95% CI; −0.94, −0.23) for carriers of two AA alleles. Heterogeneity was high and statistically significant.

Conclusions

The combined data indicate that 25OHD concentrations differ by GC rs4588 genotype in healthy adults with predominantly Caucasian ancestry with an additive effect of about 9% per allele. The much lower than average 25OHD concentrations in the about 8% GC rs4588 AA genotype carriers should draw attention to this commonly ignored group when it comes to health risks related to vitamin D deficiency.

Funding Sources

UNC Nutrition Research Institute internal support

SUBMITTER: Baah E

PROVIDER: S-EPMC8181666 | biostudies-literature |

REPOSITORIES: biostudies-literature

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