Relationship of LRP5rs121908669(G171R) genotypes to femur T-score values

Abstract

Background and aims: Among some studied cases, there is a decrease in bone mineral density in the femoral region without decrease in bone mineral density in the lumbar region in postmenopausal women. The femoral bone is mostly cortical bone. The lrp5 gene is closely related to the cortical bone. LRP5G171R(LRP5rs121908669)  is a proven pathogenic single nucleotide polymorphism SNP for a disease associated with high bone mass HBM. There is no genotyping study for it until now. There is no idea  about its relationship with other cases of BMD. Methods: LRP5rs121908669 was diagnosed using  PCR-RFLP and DNA sequencing in Syrian pre &post-menopuasal women. Related-Samples McNemar Change Test was used under 95% confidence level (α ≤ .050) to study distribution LRP5G171R genotypes  across femur T-score values. Odds Ratio test was used to identify the odd risk for femur T-score  values when LRP5G171R  genotype is absence or existed. Chi-Square Tests(ꭓ2) were used to estimate the correlation between genotypes and each of femur T- score under 95% confidence (α ≤ .050). Results: Significant chance to occurrence GG genotype, CC genotype, GC genotype  in normal, osteopenia, osteoporosis femur T –score values are ( GG 2.5%, 0.00%, 0.00%,  CC  0.00%, 0.01%, 28%, GC 0.00%, 8.7%, 57.5%),respectively.  There are significant correlation between   GG genotype  and  normal, osteopenia femur T –score values, but no significant correlation with osteoporosis femur T –score values ꭓ2=13.750, p = . 000< .05,  ꭓ2=10.765, p = . 001< .05, ꭓ2= .689, p=.407> .05, respectively. There are significant correlation between CC genotype and  normal, osteopenia femur T –score values, but no significant correlation with osteoporosis femur T –score values with ꭓ2=.683, p = . 003< .05, ꭓ2= 7.731, p = . 005< .05, ꭓ2=.204, p = . 651> .05, respectively. There are no significant correlation between GC genotype  and normal, osteopenia, osteoporosis femur T –score values with  ꭓ2= 3.463, p = . 063> .05,  ꭓ2= 2.263, p = . 133> .05, ꭓ2=  .344, p = . 557> .05, respectively. Discussion: It is the  first genotyping of LRP5G171R  in the world. Normal genotype GG increase the likelihood of normal femur BMD. homozygous genotype CC  and  heterozygous GC genotype increase the likelihood of osteoporosis or osteopenia  in femur bone. There are often associations in the distribution between carriers of GC or CC and carriers with osteoporosis or osteopenia in femur bone. Conclusion: In general, LRP5G171R is not only related to HBM, it is related to normal, osteopenia, osteoporosis. Thus, NCBI should be informed that LRP5G171R should be classified clinically as conflicting information, not pathogenic to ADO1 as it  is classified until now. Also,  LRP5G171R can be added as a risk factor within the FRAX application. LRP5G171R can be both a diagnostic and a therapeutic goal for osteoporosis.