Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women

ABSTRACT

Objectives Age at menarche (AAM), the time of the first menstrual bleeding, is an important developmental milestone in the female life. It marks the beginning of the reproductive period. AAM is implicated in the risk of many health complications in later life. In this study, we conducted an analysis for association of single nucleotide polymorphisms (SNPs) and common haplotypes of two candidate genes, RANK (receptor activator of the NF-κB) and RANKL (receptor activator of the NF-κB ligand), with AAM in 825 unrelated Chinese women.

Methods In total, 73 SNPs of RANKL and 23 SNPs of RANK were genotyped. The SNPs and common haplotypes were then analyzed for their association with AAM. Age and age were used as covariates.

Results We found five individual SNPs (rs7239261, rs8094884, rs3826620, rs8089829, and rs9956850) of RANK significantly associated with AAM (p < 0.05). Although no significant association was identified for the RANKL gene, three polymorphisms showed nearly significant (0.05 < p < 0.08) association with AAM. Seven haplotypes of RANK were significantly associated with AAM (p < 0.05); the most significant association of the AT haplotype composed by rs1805034 and rs4524034 (p = 9.4 × 10⁻⁴) remained significant (p = 0.0235) after the Bonferroni correction for multiple testing. Three haplotypes of RANKL were significantly associated with AAM (p < 0.05). Importantly, the association of rs3826620 replicated our previous findings for Caucasian females.

Conclusions The results of the present study suggest that the RANK and RANKL are two candidate genes for AAM in Chinese women.

Key words::

• AGE AT MENARCHE
• SINGLE NUCLEOTIDE POLYMORPHISMS
• ASSOCIATION
• RANK
• RANKL
• HAPLOTYPES

Conflict of interest The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Source of funding Investigators in this work were partially supported by grants from NIH (R01 AR050496-01, R21 AG027110, R01 AG026564, and P50 AR055081). The study also benefited from 211 State Key Research Fund by Hunan Normal University and the University of Hong Kong start-up fund (to V.D.).