ABSTRACT
Objective To investigate the association between single nucleotide polymorphisms ( SNPs) of FOXO1 gene and type 2 diabetic nephropathy(T2DN). Methods A total of 654 Chinese Han patients with type 2 diabetes mellitus (T2DM;394 without and 260 with T2DN) were enrolled. Six FOXO1 gene tags SNPs were selected using the Hapmap database. The genotypes of six SNPs in FOXO1 were determined by PCR-RFLP, and the clinical characteristics of the subjects were also evaluated. The interaction of SNPs with these clinical factors was analyzed by multiple factor reduction(MDR) method. Results After adjusting for age, gender, DM course, body mass index ( BMI ) , HbA1C , total cholesterol ( TC ) , triglycerides ( TG ) , high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , hypertension history, DM family history, smoking, and drinking, FOXO1 rs17446614 variant genotype was significantly associated with an increased risk of T2DN, while rs17446593 variant genotype was associated with a decreased T2DN risk. In the stratified analysis of risk factors, the correlation between rs17446614 and T2DN was unrelated with patient' s gender, hypertension history, and blood TC level. Simultaneously, rs17446614 variant genotype significantly increased the risk of T2DN in people older than 60 years,BMI less than 24 kg/m2 , LDL-C less than or equal to 3. 5 mmol/L , or DM family history. rs2721068 variant genotype significantly decreased the risk of T2DN in people less than 60 years old or without DM family history. rs2951787 variant genotype significantly increased the risk of T2DN in people with DM duration longer than 10 years or with DM family history. A variant genotype rs17592236 significantly increased the risk of T2DN in male or TC higher than 5 mmol/L. A variant genotype rs17446593 significantly decreased the risk of T2DN in male or those DM duration longer than 10 years, or BMI≥24 kg/m2 . The interactions among rs17446614, DM duration, TC, and hypertension history were also observed. Conclusion The genetic variants rs17446614, rs2721068, rs2951787, rs17592236, and rs17446593 in FoxO1 may contribute to the risk of T2DN in T2DM patients.
ABSTRACT
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Alveolar RMS (ARMS) is characterized by FOXO1-related chromosomal translocations that result in a poorer clinical outcome compared with embryonal RMS (ERMS). Because the chromosomal features of RMS have not been comprehensively defined, we analyzed the clinical and laboratory data of childhood RMS patients and determined the clinical significance of chromosomal abnormalities in the bone marrow. METHODS: Fifty-one Korean patients with RMS < 18 years of age treated between 2001 and 2015 were enrolled in this study. Clinical factors, bone marrow and cytogenetic results, and overall survival (OS) were analyzed. RESULTS: In total, 36 patients (70.6%) had ERMS and 15 (29.4%) had ARMS; 80% of the ARMS patients had stage IV disease. The incidences of bone and bone marrow metastases were 21.6% and 19.6%, respectively, and these results were higher than previously reported results. Of the 40 patients who underwent bone marrow cytogenetic investigation, five patients had chromosomal abnormalities associated with the 13q14 rearrangement. Patients with a chromosomal abnormality (15 vs 61 months, P=0.037) and bone marrow involvement (17 vs 61 months, P=0.033) had a significantly shorter median OS than those without such characteristics. Two novel rearrangements associated with the 13q14 locus were detected. One patient with concomitant MYCN amplification and PAX3/FOXO1 fusion showed an aggressive clinical course. CONCLUSIONS: A comprehensive approach involving conventional cytogenetics and FOXO1 FISH of the bone marrow is needed to assess high-risk ARMS patients and identify novel cytogenetic findings.