Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1 is thought to play an important role in the development of atherosclerosis, it remains unclear whether polymorphisms of ET-1 family genes, including the ET-1 gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2 (ECE1 and ECE2), are associated with the progression of atherosclerosis. We investigated the relationship between 11 single nucleotide polymorphisms (SNPs) of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four in ECE1 and one in ECE2) and atherosclerotic changes assessed using pulse wave velocity (PWV) and carotid ultrasonography in 630 patients with essential hypertension (EHT). In male subjects, we found significant differences in brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after Bonferroni correction. Also in male subjects, there were significant differences in mean intima-media thickness (IMT) in additive and recessive models in EDNRA-rs5333 after Bonferroni correction. We found no significant correlation between any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female subjects. Furthermore, after multiple logistic regression analysis, only EDNRB-rs5351 indicated as an independent risk of atherosclerosis in male hypertensive subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients.

Progression of avascular necrosis of femoral head and choice of treatment.

Observations of the disease course mainly by X-ray were made in 52 patients (85 joints) with avascular necrosis of the femoral head to determine the prognosis and to decide on treatment. The progression of the necrotic area is related to the activity of the original disease, to the size of the necrotic area in the early stages of the disease, and to whether or not the patient received steroid treatment. On the basis of the size and location of the necrotic area, the disease process is divided into four stages, I to IV. The affected heads are also classified into six types according to their site and extent, the degree of flatness of their weightbearing surface, and the presence of cystic lesion. Preventive treatment and conservative observation or transtrochanteric anterior rotational osteotomy and vascularized pedicle bone graft are applicable to cases in Stages I and II. Total hip joint arthroplasties and salvage procedures are performed in Stages III and IV. The usefulness of 99mTc bone scintigraphy was unexpectedly disappointing for diagnosis of the stages of the disease. However, MRI was sensitive for the diagnosis in the early stages of the disease.