XbaI and PvuII Polymorphisms of Estrogen Receptor 1 Gene in Females with Idiopathic Scoliosis: No Association with Occurrence or Clinical Form

Abstract

IntroductionXbaI single nucleotide polymorphism (SNP) (A/G rs934099) in estrogen receptor 1 gene (ESR1) was described to be associated with curve severity in Japanese idiopathic scoliosis (IS) patients and in Chinese patients with both curve severity and predisposition to IS. PvuII SNP (C/T rs2234693) of ESR1 was described to be associated with the occurrence of IS in the Chinese population; however, two replication studies did not confirm the findings. The ESR1 SNPs have never been studied in Caucasian IS patients.MethodsCase-control study. 287 females with IS underwent clinical, radiological and genetic examinations. The patients were divided into three groups according to curve progression velocity: non-progressive IS, slowly progressive IS (progression <1° per month), and rapidly progressive IS (progression ≥1° per month). The radiological maximum Cobb angle was measured and surgery rate established. A control group consisted of 182 healthy females.ResultsAll results followed Hardy-Weinberg equilibrium. In the case-control study, genotype frequency in the patients did not differ for the XbaI (AA = 33.5%, AG = 49.1%, GG = 17.4%), nor for the PvuII (TT = 26.8%, TC = 50.2%, CC = 23.0%) comparing to controls (AA = 33.5%, AG = 50.5%, GG = 15.9%) and (TT = 23.1%, TC = 51.1%, CC = 25.8%), respectively, p = 0.3685, p = 0.6046. The haplotype frequency for the patients (AT = 47.1%, GC = 39.2%, AC = 8.9%, GT = 2.8%) did not differ from the controls (AT = 44.8%, GC = 37.4%, AC = 14.0%, GT = 3.8%), p = 0.0645. No difference was found either in XbaI (p = 0.8671) or PvuII (p = 0.3601) allele distribution between the patients and the controls. In the case study, there was no significant difference in genotype frequency for the non-progressive, slowly progressive, and rapidly progressive scoliosis. No difference was found in genotype or haplotype distribution for the mean maximum Cobb angle or the surgery rate.ConclusionsNo association was found between ESR1 XbaI or ESR1 PvuII SNP and idiopathic scoliosis in Caucasian females. None of the previously reported associations could be confirmed, regarding curve severity, progression or operation rate.

Association between the ESR1 -351A>G single nucleotide polymorphism (rs9340799) and adolescent idiopathic scoliosis: a systematic review and meta-analysis

“…Subsequent studies with larger sample sizes were unable to replicate this initial finding [9][10][11]. In the present meta-analysis of these four studies (n = 1,827 AIS cases and 1,253 controls) [8][9][10][11], a non-significant association was found, suggesting that the rs9340799 SNP is not a likely susceptibility locus for AIS when examined in isolation.…”

“…One otherwise eligible study did not report the allele/genotype frequency distributions, having detected a significant deviation from HWE in the controls, and was excluded from review [21]. Two studies were conducted in Chinese populations [8,9], one in a Japanese population [10], and one in a Polish Caucasian population [11]. Three studies recruited only female cases and controls [9][10][11], whereas the study by Wu et al [8] recruited cases at a female-to-male ratio of approximately 10.9:1 and controls at 7.7:1.…”

“…Two studies were conducted in Chinese populations [8,9], one in a Japanese population [10], and one in a Polish Caucasian population [11]. Three studies recruited only female cases and controls [9][10][11], whereas the study by Wu et al [8] recruited cases at a female-to-male ratio of approximately 10.9:1 and controls at 7.7:1. Deviation from HWE was detected in the control subjects of the Wu et al [8] study.…”

“…Thus, potential for selection bias cannot be adequately assessed. Proper genotyping methods were used in all the studies, but only two studies applied any form of genotyping quality control procedures [9,11] and none blinded to case-control status when genotyping. Population stratification may confound the genetic association by masking true associations or creating spurious associations: a possibility in the Wu et al [8] study, which included HWE-deviated controls, and also in studies with apparently homogeneous ethnic groups [25].…”

“…Recently, the rs9340799 SNP was investigated in several candidate gene association studies of AIS risk. However, findings were mostly negative [8][9][10][11]. With limited sample sizes, power analysis found that these studies lacked adequate statistical power (\80 %) to detect weak associations (odds ratio equal to approximately 1.2) typically observed for common genetic variants [12], such as rs9340799 [13].…”