Table 1.
Recent studies of G*E interactions with osteoporosis-related phenotypes in humans
| Gene | Tested marker(s) | Sample: age, sex, ethnic composition | Phenotype (skeletal site for BMD; how OP was defined) | Main effect: OR or RR aP value b | Interaction | Ref. |
|---|---|---|---|---|---|---|
| APOE | Alleles ε2/ε3/ε4 | Scottish women, early postmenopausal (n=2721) | LS BMD, FN BMD; BMD change | P≤0.05 for LS BMD and change in LS BMD | Tested for an interaction between the APOE polymorphism and dietary vitamin Kl intake | [78] |
| COLIA1 | –1997G/T (rs1107946),- 1663in/delT (rs2412298), and +1245G/T | 1717 Caucasian perimenopausal women (age 50.0±2.9 y) | LS BMD, Hip BMD; All Frx & vertebral Frx; turnover markers (25-hydroxyvitamin D, osteocalcin, bone specific alkaline phosphatase, hydroxyproline) | P<.05-0.005 | No association with pMP change in BMD (10-y follow-up), fracture risk; no interaction with the hormone therapy | [79] |
| ESR1 | 4 SNPs, incl. rs2077647 and rs2234693 | Japanese women (cases: 114 postmenopausal with a confirmed osteoporosis) and controls: 171 healthy (mean age of 39.0 y) | Osteoporosis risk | OR = 3.15, 95 % CI = 1.83-5.41 (Haplotype of 2 SNPs) | Statistically significant interaction (P=0.03) with alcohol drinking | [80] |
| IL6 | –634C/G | 176 Chinese girls aged 9–11 y (Pre-menarche) | BMD and BMC at total body, total hip and FN | <0.05 | Interactions observed with physical activity (P<0.05) and calcium intake | [81] |
| LRP5 | 4 SNPs (incl. rs4988321) | Greek postmenopausal women (n = 578); stratified by calcium intake revealed that in the low calcium intake group (at 680 mg/d) | LS and hip BMD osteoporotic Frx | rs4988321 with LS BMD (P=0.002) | Interaction of the rs4988321 with calcium intake (P=0.016); In low calcium intake group, rs4988321 Associated with LS BMD (P=0.001) | [82] |
| MTHFR | rs1801133 (C677T) | 5035 Dutch men and women, age 55+ y-old | Fracture | n.s. | Found interaction with dietary riboflavin intake on Frx risk | [83] |
| MTHFR | rs1801133 (C677T) | 5816 U.K. Caucasian children, 9.9 y-old | BMD: total body less head region (N=5816), lumbar spine (N=3196) | P<0.001 (spine BMD) | SNP*sex interaction: P=0.04 (spine BMD) | [84] |
| PPARG | 13 SNPs (incl. rs2028760, rs1801282, rs1805192) | US Caucasian men (n=867, 62.2±9.1 y) and women (n=925, 60.5±9.1 y) | FN, TR, and LS BMD | <0.05 (mostly in men with FN) | Interaction with dietary fat intake on BMD: rs1151999 & rs709150 in men and rs1175381 and rs1186464 in women. | [27] |
| PPARG | 10 SNPs (incl. rs12497191, rs4135263, rs1151999, and rs1152003) | 2 Danish cohorts: a case-control (n=809) and 1716 perimenopausal women allocated to hormone therapy or not at baseline and followed for 10 y | vertebral Frx; LS & FN BMD | VertFrx risk (OR= 1.48-1.76, P=0.005-0.04 for rs12497191, rs4135263, and rs1151999) increased BMD (P≤0.02 for rs1151999) | An interaction between rs1151999 and diet and rs1152003 and weight on BMD | [85] |
| VDR | BsmI, TaqI and Cdx-2 | Greek postmenopausal women (n=578); stratified by calcium intake | LS & hip BMD osteoporotic Frx | n.s. | In low calcium intake group (<680 mg/d), all variants were associated with LS BMD (P<0.05) | [86] |
BMC bone mineral content, BMD bone mineral density, CI confidence interval, FN femoral neck, Frx fracture, LS lumbar spine, m.s. marginally significant, n.s. nonsignificant, OP osteoporosis, OR odds ratio, PMP postmenopausal (women), RR risk ratio, TR trochanter
a
OR and 95 % CI
b
Statistical significance: when there are more than one phenotype or SNP, lowest P value is provided