Table 3.
Single-Nucleotide Variants Detected by Sequencing ALPL in Groups of Men Selected for Low or Normal Serum ALP Activity, Osteoporotic Fractures in Men (MrOS) Study
| Group 1, selected for low ALP (n=74) | Group 2, selected for normal ALP (n=148) | ||||
|---|---|---|---|---|---|
| ALP (U/L) | |||||
| Mean (SD) | 34.2 (4.9) | 71.8 (1.1) | |||
| Range | 19.0–39.0 | 70.0–74.0 | |||
| Phosphate (mg/dL) | 3.33 (0.48) | 3.20 (0.48) | |||
| n (%) | n (%) | pa | |||
| Any variant (25 variants) | 45 (60.8%) | 65 (37.1%) | 0.0006 | ||
| Any variant with MAF ≥ 1% (3 variants) | 28(37.8%) | 49 (33.1%) | 0.49 | ||
| Any variant with MAF<1% (22 variants | 27(36.5%) | 5 (3.4%) | 1.6 × 10−10c | ||
| Variants detectedb | n (%) | n (%) | MAF (%) | pc | |
| Synonymous (four variants) | 20 (27.0) | 32 (21.6) | NA | 0.40 | |
| S110S | T>C | 2 (2.7) | 1 (0.7) | 0.3% | 0.26 |
| P292P | AA | 58 (78.4) | 118 (79.7) | 11.1% | 0.89 |
| AG | 15 (20.3) | 27 (18.2) | |||
| GG | 1 (1.4) | 3 (2.0) | |||
| T366T | C>G | 1 (1.4) | 0 (0.0) | d | 0.30 |
| A514A | T>G | 1 (3.2) | 2 (1.4) | 0.7% | >0.99 |
| Nonsynonymous, common (two variants) | 23 (31.1) | 45 (30.4) | NA | >0.99 | |
| Y263He | TT | 61 (82.4) | 119(80.4) | 10.1% | 0.90 |
| TC | 13 (17.6) | 28 (18.9) | |||
| CC | 0 (0.0) | 1 (0.7) | |||
| V522A | TC | 11 (14.9) | 22 (14.9) | 7.5% | >0.99 |
| Nonsynonymous, rare (19 variants) | 25 (33.8) | 2 (1.4) | NA | 9.9 × 10−12 | |
| T134He | A>C | 1 (1.4) | 0 (0.0) | d | 0.33 |
| E146Ke | G>A | 2 (2.7) | 0 (0.0) | d | 0.11 |
| R152H | G>A | 5 (6.8) | 2 (1.7) | 0.9% | 0.05 |
| S181Le | C>T | 1 (1.4) | 0 (0.0) | d | 0.33 |
| M192Te | T>C | 2 (2.7) | 0 (0.0) | d | 0.11 |
| R246Se | G>T | 1 (1.4) | 0 (0.0) | d | 0.33 |
| G249Ve | G>T | 1 (1.4) | 0 (0.0) | d | 0.33 |
| R272Ce | C>T | 2 (2.7) | 0 (0.0) | d | 0.11 |
| T273Me | C>T | 2 (2.7) | 0 (0.0) | d | 0.11 |
| F327Ce | T>C | 1 (1.4) | 0 (0.0) | d | 0.33 |
| R357Le | G>T | 1 (1.4) | 0 (0.0) | d | 0.33 |
| R391Ce | C>T | 2 (2.7) | 0 (0.0) | d | 0.11 |
| N417S | A>G | 2 (2.7) | 0 (0.0) | d | 0.11 |
| R428Qe | G>A | 1 (1.4) | 0 (0.0) | d | 0.33 |
| Y436Se | A>C | 1 (1.4) | 0 (0.0) | d | 0.33 |
| A443V | C>T | 1 (1.4) | 0 (0.0) | d | 0.33 |
| V461I | A>G | 1 (1.4) | 0 (0.0) | d | 0.33 |
| H482Ne | C>A | 1 (1.4) | 0 (0.0) | d | 0.33 |
| G491Re | G>A | 2 (2.7) | 0 (0.0) | d | 0.11 |
ALP = alkaline phosphatase; MAF=minor allele frequency; NA= not applicable.
a
For χ2, compared to the group with no variant of the same category.
b
All variants were detected as heterozygotes, except for P292P and Y263H.
c
For Fisher’s exact test.
d
Minor allele not detected in the “normal ALP” group.
e
Sequence variant resulting in a nonconservative amino acid substitution.