Search for Genetic Variant in the Apelin Gene by Resequencing and Association Study in European Subjects.

AIMS: Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants. METHODS: We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency >0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits. RESULTS: Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits. CONCLUSIONS: Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects.

BACKGROUND: Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia. METHODS: A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants. RESULTS: We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin-sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender-specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild-type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed. CONCLUSION: We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.

C1-C2 X-Ray assessment of misalignment parameters in patients with Chronic Cerebra-spinal Venous Insufficiency and Multiple Sclerosis versus patients with other pathologies.

PURPOSE: The complete compression of the internal jugular veins, in front position, shows a prevalence of 48% and it is equally distributed in the various segments of these veins in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and Multiple Sclerosis (MS). The aim of this search is to identify radiological dislocation of C1-C2 as specific markers in patients with CCSVI and Multiple Sclerosis (MS). METHOD: We investigated 386 patients suffering from CCSVI and Multiple Sclerosis and a control group of 156 patients without MS. RESULTS: The assessment of Anterior Intrusion shows the following average values: in the group with CCSVI and MS: 4.29 ±1.48 mm while in the control group: 3.78 ±1.45 mm (p = 0.0008).The evaluation of the Right Laterality shows the following average values: in group with CCSVI and MS: 2.31±1.41 mm, in control group: 1.97 ±1.28 mm (p = 0.0426). We found also that a longer duration of the disease corresponds to a higher severity of the pathological condition (p <0.0001). CONCLUSION: Data analysis of C1-C2 X-Ray parameters shows statistical significance of severe anterior intrusion and right laterality misalignment in the people with CCSVI and MS, that are two to three times more frequent as compared to controls. Considering the novelty of this work and the total absence of scientific similar works able to confirm this data, it is necessary to continue these studies in order to improve the clinical management of these patients and to perform therapeutic strategies based on venous decompressive treatments both surgical that manipulatives.