Estrogen receptor polymorphism, estrogen content and idiopathic scoliosis in human: a possible genetic linkage

Idiopathic scoliosis (IS) is a largely diffused disease in human population but its pathogenesis is still unknown. There is a relationship between scoliotic phenotype and the patient age, since in the early stage the pathology shows a ratio of 50% between male and female teenagers. During puberty the sex ratio is 8.4/1 (female/male), suggesting a sex-conditioned manifestation of the disease. Genetic inheritance of idiopathic scoliosis is still unclear although some authors claim for its X-linked dominant inheritance. There is large agreement in considering the IS as a sex-conditioned disease, in terms of steroid content and their receptor activity, although no evidence has been found yet. The blood content of 17beta-estradiol in teenagers with IS shows lower levels than teenagers of the same age without IS. Also testosterone and progesterone content are lower in IS girls with respect to the control girls. Furthermore, we extracted DNA from white blood cells of IS patients and their relatives until the third generation in order to examine estrogen receptor alpha polymorphisms, considering this tool a plausible molecular marker for IS prognosis. In this respect, we identified four polymorphisms in the exons encoding for the steroid binding domain and two other in the trans-activation domain. Our results show a clear relationship with clinical manifestation of IS.