Objective To detect the relationship between the polymorphism of the glycogen-targeting regulatory subunit of the skeletal muscle glycogen-associated protein phosphatase 1 (PPP1R3) gene and type 2 diabetes by case-control study. Methods We genotyped the PPP1R3 gene Asp905Tyr polymorphism and a common 3'-untranslated region AT (AU)-rich element (ARE) polymorphism in 101 type 2 diabetic patients and 101controls by oligonucleotide ligation assay (OLA) and polyacrylamide gel elecrophoresis, respectively. Results Subjects with Tyr/Tyr genotypes whose body mass index (BMI)<25 were used as the reference group. Those whose BMI25 with Asp905 had a 3.66-fold increase (95% CI: 1.48-9.06, P=0.005) in type 2 diabetes risk. No association was found between 3'UTR ARE polymorphism and type 2 diabetes mellitus (OR=1.15; 95% CI: 0.62-2.14, P=0.65). Conclusion A joint effect between the Asp905 and BMI increases the risk of type 2 diabetes, and Asp905Tyr and ARE polymorphism of PPP1R3 gene are not the major diabetogenic gene variants in Chinese population.

OBJECTIVETo determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the beta(3)-adrenergic-receptor (beta(3)-AR) gene with type 2 diabetes mellitus (DM) and its intermediate phenotypes in the Chinese population.

METHODSPolymerase chain reaction-oligonucleotide ligation assay and restriction fragment length polymorphism assay were used to evaluate the GYS1 and beta(3)-AR gene polymorphisms in 102 pairs of case-control Chinese spouses.

RESULTSSubjects with Met416Val variant had a significantly higher 2-hour post-glucose level than subjects without this variant had in diabetic group (P = 0.032). The Met416Val polymorphism of GYS1 gene was not significantly associated with the risk of type 2 DM (adjusted OR = 1.67; 95% CI: 0.73 - 3.81, P = 0.223). Subjects with Trp64Arg variant had a significantly higher serum uric acid level than subjects without this variant had in diabetic group (P = 0.034). The combination of BMI and Arg64 allele carrier of the beta(3)-AR gene increased the diabetic risk over four-fold (adjusted OR = 4.00; 95% CI: 1.53 - 10.45, P = 0.005).

CONCLUSIONSIn the Chinese population, Met416Val polymorphism is identified in a subgroup of diabetic subjects with high 2-hour post-glucose. It will explain why some diabetic patients appear to be genetically predisposed to developing high postpradial glucose level. The presence of the Arg64 allele in the beta(3)-AR gene may predispose patients to higher serum uric acid level.

Adult ; Aged ; Alleles ; Body Mass Index ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Glycogen Synthase ; genetics ; Humans ; Hyperglycemia ; genetics ; Middle Aged ; Polymorphism, Genetic ; Postprandial Period ; physiology ; Receptors, Adrenergic, beta-3 ; genetics ; Uric Acid ; blood

Objective:To evaluate the safety and efficacy of vemurafenib in the treatment of BRAF V600E-mutated Erdheim-Chester disease (ECD) . Methods:We retrospectively analyzed the clinical data, response rate, adverse events and survival of 12 patients with ECD treated with vemurafenib from March 2015 to October 2020 in Peking Union Medical College Hospital.Results:Of 12 patients [7 males and 5 females, median age = 51.5 (range, 32-66) years old], the median number of organs involved was 6 (range, 4-8) , and the median treatment duration of vemurafenib was 11 (3-60) months. All patients had improvement of clinical symptoms, of which 2 cases were completely relieved, and 10 cases were partially relieved. Seven patients evaluated by 18F-FDG-positron emission tomography/computed tomography achieved a metabolic response, including 2 patients with a complete metabolic response and 5 patients with a partial metabolic response. The common adverse events in the overall cohort were grade 1 to 2 (Common Terminology Criteria for Adverse Events 5.0) , including skin rash (58.3%) , arthralgia (25.0%) , and digestive tract reactions (16.7%) . The median follow-up time was 13.5 (3-60) months. One patient with central nervous system involvement died due to a cerebrovascular event, and one patient relapsed 10 months after drug withdrawal. The estimated 2-year overall survival rate and 2-year progression free survival rate were 88.89% and 66.67%, respectively. Conclusions:Vemurafenib is safe and effective in the treatment of BRAF V600E-mutated ECD.