Replication Study Confirms the Association of the Common rs1800629 Variant of the TNFα Gene with Postmenopausal Osteoporosis Susceptibility in the Han Chinese Population

Abstract

We have shown that a TNFα gene polymorphism, rs1800629, is highly significantly associated with postmenopausal osteoporosis and BMD in the female Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this genomic region and its relationship with osteoporosis-related phenotypes.

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

“…Therefore, the exact underlying mechanisms of how this SNP affects the expression of TNF‐α and hence affects development of osteoporosis are still unclear and further functional investigation is needed to clarify these issues. Additionally, it should be noted that several included studies reported inconsistent findings for the effect of G308A polymorphism on osteoporosis . The reason might be ascribed to the ethnic differences of each study.…”

“…Nine studies evaluated the associations between TNF-α G308A polymorphism (GG vs GA+AA) and BMD, in which eight studies focused on LS-BMD [9][10][11][12]15,16,19,21 and six studies focused on FN-BMD [10][11][12][13]15,16 (Figure 3). According to the results, the mutant genotypes did not significantly affect the BMD as compared with GG genotype based on either LS-BMD data (P = 0.55, I 2 = 60%) or FN-BMD data (P = 0.37, I 2 = 91%).…”

“…Five studies evaluated the association between TNF-α G308A polymorphism (GG vs AA) and LS-BMD, 10,11,15,16,19 which exhibited significant association based on overall analysis (P = 0.04, I 2 = 84%; Figure 5). As shown in Figure 5, the AA genotype significantly increased the BMD of lumbar spine (P = 0.01, I 2 = 53%).…”

“…In contrast, several other studies indicated that TNF‐α G308A had no significant influence on BMD . Furthermore, studies regarding the associations between TNF‐α gene polymorphisms and risk of osteoporosis also exhibited inconsistent conclusions . Therefore, there is a high degree of uncertainty with respect to the exact impact of TNF‐α gene polymorphisms on BMD values and osteoporosis risk, the elucidation of which still requires a general summary in addition to clinical studies.…”

“…9,13 Furthermore, studies regarding the associations between TNF-α gene polymorphisms and risk of osteoporosis also exhibited inconsistent conclusions. 12,[14][15][16] Therefore, there is a high degree of uncertainty with respect to the exact impact of TNF-α gene polymorphisms on BMD values and osteoporosis risk, the elucidation of which still requires a general summary in addition to clinical studies. Nevertheless, no such systematic investigation has been performed so far as we know.…”