Table 3.
Associations of SNPs at SOD2 Locus with Hip BMD and with SOD2 mRNA Expression Level
| rs12192410 | rs10455776 | rs2053949 | rs11968525 | rs12525670 | rs9355741 | rs7754103 | rs7754295 | |||
|---|---|---|---|---|---|---|---|---|---|---|
| 1Allele A/B | G/A | A/C | C/T | T/C | T/C | A/G | A/G | A/G | ||
| 2MAF | 0.18 | 0.07 | 0.41 | 0.19 | 0.18 | 0.29 | 0.10 | 0.10 | ||
| β Values of Association with Hip BMD | 8.23E-03 | 1.26E-02 | −6.94E-03 | 9.50E-03 | 9.31E-03 | −8.03E-03 | 1.14E-02 | 1.11E-02 | ||
| P Values of Association with Hip BMD | 9.10E-02 | 9.42E-02 | 7.39E-02 | 4.83E-02 | 5.44E-02 | 5.31E-02 | 7.18E-02 | 7.76E-02 | ||
| Mean BMD (g/cm2) | AA | 0.931 | 0.991 | 0.914 | 0.942 | 0.937 | 0.903 | 1.005 | 1.005 | |
| Stratified by Genotypes | AB | 0.923 | 0.917 | 0.920 | 0.920 | 0.922 | 0.920 | 0.920 | 0.919 | |
| BB | 0.919 | 0.920 | 0.922 | 0.919 | 0.918 | 0.923 | 0.920 | 0.919 | ||
| Genotypic Effect of SNP on BMD (BB vs. AA)3 | ↓ | ↓ | ↑ | ↓ | ↓ | ↑ | ↓ | ↓ | ||
| P Value of eQTL Analyses | 215078_at | NS | NS | NS | 8.47E-02 | 8.47E-02 | NS | NS | NS | |
| 215223_s_at | NS | NS | 2.97E-02 | NS | NS | 6.47E-02 | NS | NS | ||
| 216841_s_at | NS | NS | 3.35E-02 | NS | NS | NS | NS | NS | ||
| 221477_s_at | NS | NS | 8.70E-02 | NS | NS | NS | NS | NS | ||
| 1566342_at | NS | NS | 2.18E-01 | NS | NS | NS | 2.60E-02 | 2.60E-02 | ||
| Mean Expression Levels Stratified by Genotypes | 1566342_at | AB/BB | 5.14/5.21 | 5.31/5.15 | 5.17/5.05 | 5.10/5.24 | 5.10/5.24 | 5.28/5.02 | 4.83/5.26 | 4.83/5.26 |
| 221477_s_at | AB/BB | 9.25/9.60 | 9.42/9.49 | 9.40/9.29 | 9.25/9.63 | 9.25/9.63 | 9.61/9.23 | 9.04/9.57 | 9.04/9.57 | |
| 216841_s_at | AB/BB | 7.82/8.24 | 7.83/8.16 | 8.09/7.64 | 7.83/8.26 | 7.83/8.26 | 8.25/7.80 | 7.83/8.14 | 7.83/8.14 | |
| 215223_s_at | AB/BB | 9.17/9.81 | 9.32/9.65 | 9.49/9.03 | 9.16/9.86 | 9.16/9.86 | 9.87/9.06 | 8.95/9.71 | 8.95/9.71 | |
| 215078_at | AB/BB | 5.33/6.47 | 5.56/6.20 | 5.96/5.49 | 5.26/6.60 | 5.26/6.60 | 6.53/5.23 | 4.90/6.31 | 4.90/6.31 | |
| Genotypic Effect of SNP on Expression (BB vs. AB)4 | ↑ | ↑ | ↓ | ↑ | ↑ | ↓ | ↑ | ↑ | ||
Alleles A and B represent minor and major alleles, respectively;
MAF: minor allele frequency in the study sample;
↑ & ↓ increased & decreased BMD in carriers of genotype BB vs. AA;
↑ & ↓ increased & decreased mRNA expression in carriers of genotype BB vs. AB. In the sample for eQTL analyses (N=22), no homozygous minor allele was observed for the SNPs, except SNP rs2053949 with two AA carriers). For all the eight SNPs, the trend of association for SNP and mRNA expression is reverse to that for SNP and BMD. Such findings are consistent with the negative correlation between SOD2 gene expression and BMD observed at both mRNA and protein levels, i.e., higher SOD2 gene expression, lower BMD (Table 2). NS: not significant.