Estrogen receptors genes polymorphisms and age at menarche in idiopathic scoliosis

Abstract

Background: The age at menarche (AAM) is commonly in use in patients with IS as one of the maturity indicator suggesting deceleration of the growth velocity. The AAM was suggested to be related to predisposition and curve progression potential of IS. The late age at menarche was reported to be associated with higher prevalence of adolescent idiopathic scoliosis. The age at menarche is determined by both genetic and environmental factors as well as their interactions. Estrogen receptors 1 and 2 polymorphism were reported to be associated with AAM: in ESR1 XbaI and PvuII site polymorphism and in ESR2 AluI site polymorphism.The purpose of the study was to investigate associations of the ESR1 and ESR2 polymorphisms with AAM in IS patients and to evaluate association of AAM with IS severity.

Methods: 208 females with IS Caucasian females from Central Europe underwent clinical, radiological and genetic examinations. Four SNPs were selected XbaI (A/Grs9340799) and PvuII (C/T rs2234693) in ESR1and AluI (A/G rs4986938) and RasI (A/G rs1256049) in ESR2. Samples were analyzed with polymerase chain reaction followed by restriction fragments length polymorphism analysis (PCR-RFLP). The age of a menarche was established during personal interview with the patients and in case of children with their parents. The Cobb angle was measured.

Results: All genotypes followed HWE. Mean AAM for patients was 154.8 ± 14.7 months (12.9 ± 1.2 years). The earliest AAM was 121 and latest 192 months. There was no statistically significant difference between AAM mean values in each genotype, for the XbaI, PvuII, AluI and RsaI site polymorphisms the p values were p=0.7141, p=0.9774, p=0.7973 and p=0.2282, respectively. Patients divided according to Cobb into mild (<30°), moderate (30°-49°) or severe (≥ 50°) IS revealed tendency to delay AAM: 151.9 ± 14.7; 155.2 ± 14.8 and 157.9 ± 14.0 months, respectively. There was statistical significant difference between patients with mild <30° and severe ≥ 50° IS, p=0.0267.

Conclusions: In IS patients estrogen receptors polymorphisms did not show association with the AAM. Patients with severe IS form revealed delayed AAM than patients with mild IS form.

Figure 1

Example of PCR products electrophoresis for ESR2 rs4986938 M – Nova 100 bp DNA ladder size standard (Novazym®), 1–8 – patients DNA.

Figure 2

Example of AluI enzyme RFLP products electrophoresis for ESR2 rs4986938 1–8 – patients’ DNA. M - Nova 100 bp DNA Ladder size standard (Novazym®) (samples 1 and 4 were homozygotes AA genotype – in both alleles enzymatic restriction occurred; sample 5–7 - was homozygote GG genotype – in both alleles enzymatic restriction did not occur; samples 2,3 and 8 – were heterozygotes AG genotype – in one allele enzymatic restriction occurred and in the other did not).

Figure 3

The mean age at menarche in patients divided according to Cobb angle, p > 0.05.