Supplemental Table 5. Overview of associations between CYP2R1 gene polymorphisms and 25(OH)D levels reported in the literature.

Authorref / Population / N / Assay / SNPs / Difference reported
Wang
2010 [9] / Healthy
European / Total: 33996
Discovery cohort:
16125
Replication cohort
9367
De novo replication cohort 8504 / Chemiluminescence
Immunoassay
Or
Radioimmunoassay
Or
ELISA (IDS)
Or
Liquid Chromatography Tandem Mass Spectrometry / rs10741657 / OR (95% CI) 1.2 (1.21-1.29)
for having 25(OH)D below 30 ng/ml per copy of the risk allele, adjusted for age, sex, BMI and season: Difference up to 2.4 ng/ml between genotypes
Bu
2010 [11] / Healthy
White / Total 496
Discovery cohort
66 men,
90 women,
Replication cohort
340 women, / Radioimmunoassay / rs12794714
rs10766197
rs2220220
rs1562902 / Difference up to 2.8 ng/ml in the discovery cohort for the four SNPs (R2 4%-8%).
Difference up to 1.76 ng/ml in the replication cohort for rs12794714, rs10766197, and rs2220220 SNPs (R2 1%-2%).
Difference up to 2 ng/ml (R2 3%) in the pooled dataset
Ahn
2010 [12] / Healthy
European / Total 6722
Discovery cohort
4501
Replication cohort 2221 / Chemiluminescence
Immunoassay
or
Radioimmunoassay / rs2060793 / Difference up to 3.6 ng/ml between genotypes, adjusted for age, vitamin D assay batch, study, case–control status, sex, BMI, season of blood collection, vitamin D supplement intake, dietary vitamin D intake, latitude
Elkum
2014 [13] / Healthy
-Arabs
-South Asians
-Southeast Asians / Total 1549 / Chemiluminescence Immunoassay / rs10500804
rs12794714
rs10741657 / Difference up to 2.4 ng/ml between genotypes for rs10500804 and rs12794714 in Arabs
Difference up to 2.8 ng/ml for rs10741657 in South Asians
No significant difference in SouthEast Asians
Ramos-Lopez
2007 [14] / Type 1 diabetes
Germans / Total 133
Men to women ratio: 1:1.03 / Radioimmunoassay (Diasorin) / rs12794714
rs10741657 / Difference up to 15 ng/ml between genotypes for rs10741657
Difference up to 5 ng/ml for rs12794714, but the difference was not significant for this SNP
Simon
2011 [15] / Multiple sclerosis & healthy controls / 1,655 cases
6,349 controls.
Women / Not specified / rs10741657 / Difference of 2.1 ng/ml per low frequency variant allele
Zhang
2013 [16] / Healthy
Chinese / Total 2897
2304 women
593 men / Automated Roche Electrochemiluminescence system / rs10766197 / Difference up to1.6 ng/ml between genotypes
OR for having 25(OH)Dbelow 20 ng/ml: 1.2 per copy of the risk allele
Ye 2015 [19] / Compilation of European populations
Diabetes type 2 cases and non cases / 217859 non-cases
36636 cases / Radioimmunoassay / rs10741657 / -1.28 ng/ml per risk allele
Barry
2014 [20] / Healthy
White / Total 1787
64% males / Radioimmunoassay (Immunodiagnostic Systems) / rs12794714
rs10741657
rs1562902
rs10766197 / Estimated percentage difference (95% CI) per low frequency variant allele compared to the major polymorphism adjusted for age, sex and season.
-4.7% (-6.6, -2.7)
4.9% (2.7, 7.1)
3.3%(1.2, 5.4)
-3.8% (-5.7, -1.8)
Sollid 2015 [22] / Norvegians with prediabetes / Total 484
186 females & 298 males / Not specified / rs10741657 / 1.72 ng/ml difference between homozygous for the major polymorphism and homozygous for the low frequency gene variant
Robien 2013 [35] / Middle-aged and elderly Chinese in Singapore / Total 63257
56% women / Chemiluminescence immunoassay / rs1993116
rs10741657rs12794714 / +2.04 ng/ml per rs10741657 in homozygous for the low frequency gene variant vs. homozygous for the major polymorphism
-4.2 ng/ml per rs12794714 in homozygous for the low frequency gene variant vs. homozygous for the major polymorphism
Lafi 2015 [42] / Jordanians with or without diabetes / Total 381
74 males & 307 females / Enzyme-linked immunosorbent assay / rs10741657 / +2.1 ng/ml in apparently healthy subjects that are low frequency variant allele carriers
Nissen
2014 [44] / Healthy Danish / Total 758
390 women & 372 men
344 children &
414 adults / Liquid Chromatography Tandem Mass Spectrometry / rs7116978
rs10741657
rs1562902
rs10766197 / Difference up to 4 ng/ml between genotypes in adults and up to 4.6 ng/ml between genotypes in children (4.2 ng/ml in the overall population)
Hassanein
2014 [46] / Coronary artery disease patients and healthy controls
Egyptian / 134 CAD male patients
109 healthy controls / High Performance Liquid Chromatography
HPLC-UV / rs10741657
rs12794714 / A significant difference was observed between genotypes for rs10741657 (59.6±5.2 ng/ml in those who were homozygous for the low frequency gene variant vs 31.93±4.1 ng/ml in those who were homozygous for the major polymorphism in the overall population but the difference disappeared when the analyses were done for cases and controls separately.
Current Study / Healthy / Total 218
96 men & 122 women / Liquid Chromatography Tandem Mass Spectrometry / rs1562902
rs10741657
rs10766197
rs12794714 / Difference up to 7.6 ng/ml between genotypes after adjustment for age, BMI and season. CYP2R1 polymorphisms explained between 4.8% and 9.8% of variability in 25(OH)D levels. Differences were significant in women only

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