Objective: Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor a (ERa) polymorphisms, which may influence sensitivity to estrogen, have been reported for men; the data concerning women are not conclusive. We investigated the association of common ERa polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography. Methods: ERa polymorphisms at positions c.454-397 TOC (PvuII) and c.454-351 AOG (XbaI) were studied in 157 women (age 45-88 years). The severity of CAD was assessed by the number of arteries with O50% stenosis in the angiography.Results: There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (PZ0.008); similar results were obtained for the XbaI polymorphism (PZ0.021). These associations were independent of other risk factors for CAD. Women homozygous for the C allele had significantly higher triglyceride and insulin levels; they belonged more frequently to the group with a low number of births (n%1; PZ0.014, Fisher's exact). Conclusions: Common ERa polymorphisms may influence the severity of CAD in women undergoing coronary angiography, reflecting lifetime exposure to estrogen. Similar associations have been reported for men with CAD. These polymorphisms should probably be taken into account when associations with estrogenic actions are examined. European Journal of Endocrinology 156 489-496

Objective: Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece. Patients and methods: Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened. Results: A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%). Conclusion:The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group.