Screening of AIP Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas.

Aims: Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations have long been associated with apparently sporadic pituitary adenomas (PAs) with a prevalence range of 0-12%. The aim of this study was to evaluate the frequency of germline AIP variations in a large cohort of apparently sporadic PAs diagnosed before the age of 40 years, who did not exhibit hypercalcemia and/or MEN1 syndrome components during long-term follow-up. Materials and Methods: A total of 97 patients, diagnosed with functional PAs ≤40 years old, composed of somatotropinoma (n = 55), prolactinoma (n = 25), and corticotrophinoma (n = 17), were recruited for this study. Fifty-one of these patients [somatotropinoma (n = 30), prolactinoma (n = 15), and corticotrophinoma (n = 11)] were previously reported as AIP mutation-negative by Sanger sequencing. The entire coding sequence of the AIP gene, along with exon/intron boundaries and the untranslated regions of 41 newly recruited patients, were sequenced for germline variations. In addition, all patients were subjected to multiplex ligation-dependent probe amplification to detect copy number variations in the AIP gene. Results: The AIP c.911G>A: p.Arg304Gln (rs104894190) variant was detected in only two patients with functional PA: one with somatotropinoma [in 1/55 (1.8%)] and one with prolactinoma [in 1/25 (4%)]. None of the corticotrophinomas revealed AIP gene alterations. Thus, the overall prevalence of AIP variation was 2.1% in our cohort. Conclusions: Germline AIP gene variations among Turkish patients with apparently sporadic PAs are relatively rare among patients ≤40 years old. None of the patients in our cohort revealed any obviously pathogenic AIP variants.

The relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients as evidenced by measurement of carotid intima-media thickness and soluble CD146 levels: a cross sectional study.

BACKGROUND: Detection of early vascular changes prior to clinical manifestations of atherosclerosis, such as increased arterial carotid intima-media thickness (CIMT) and impaired endothelial function is of paramount importance for early identification of subjects at increased risk of accelerated atherosclerosis. The present study was designed to evaluate the relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients based on measurements of CIMT and soluble CD146 (sCD146) levels. METHODS: Thirty-seven patients with type 1 diabetes, 14 males (37.8%) and 23 females (62.2%), of mean (SD) age 26.2 (4.1) years admitted to the outpatient diabetes clinic at Okmeydani Training and Research Hospital, Istanbul, between January 2008 and December 2012, and 37 healthy controls, 16 males (43.2%) and 21 females (56.8%), of mean (SD) age 25.8 (3.1) years, selected from relatives of patients, were included. Anthropometric measures; fasting plasma glucose; and serum HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and creatinine concentrations were compared, as were CIMT and serum sCD146. RESULTS: Mean (SD) sCD146 levels were significantly higher in patients than in controls (314.6 (141.9) ng/ml vs. 207.8 (34.5) ng/ml, p = 0.001), but mean (SD) CIMT did not differ (0.5 (0.1) mm vs. 0.4 (0.1) mm). ROC curves for sCD146 significantly differed in differentiating type 1 diabetics from healthy controls (p = 0.0047) with a significantly higher percentage of patients than controls having sCD146 levels >260 ng/ml (21/37 (56.8%) vs. 2/37 (5.4%), p = 0.00011). CONCLUSION: Our findings emphasize that sCD146 levels may be a more sensitive marker than CIMT for earlier identification of type 1 diabetic patients at high risk for atherosclerosis.