PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study.

(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus.

New emerging roles of the novel hepatokine SERPINB1 in type 2 diabetes mellitus: Crosstalk with ß-cell dysfunction and dyslipidemia.

Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-ß-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing ß-cell proliferation. However, its role in type-2-DM (T2DM) patients has not been adequately studied. This study was designed to investigate its circulating levels in subjects with/without T2DM, and to study its association with ß-cell function, as well as various glycemic-control and lipid-profile parameters. Anthropometric data and biochemical markers including fasting plasma glucose (FPG), HbA1C % and lipid profile parameters were measured in 55 T2DM patients, as well as 30 healthy nondiabetic subjects. Serum serpinB1, insulin and C-peptide levels were measured by ELISA. The homeostasis model assessment of both ß-cell function (HOMA2-ß%) and insulin resistance (HOMA-IR) were calculated. SerpinB1 levels were found to be significantly lower in T2DM patients 0.7 (0.2-12.4) ng/mL, compared to nondiabetic subjects 1.2 (0.94-24) ng/mL, P < 0.001, regardless of glycemic control, obesity, or insulin resistance. Additionally, serpinB1 levels were found to be positively associated with C-peptide, HOMA2-ß% in all subjects; and BMI only in non-DM subjects; while negatively associated with FPG, HbA1C% and lipid-profile parameters. Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of ß-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in ß-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for ß-cell proliferation.

A Novel SERPINB1 Single-Nucleotide Polymorphism Associated With Glycemic Control and ß-Cell Function in Egyptian Type 2 Diabetic Patients.

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic ß-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients. Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants with risk of diabetes, various biochemical parameters, and glycemic control in diabetic patients was assessed. Results: All genotyped subjects were found to be homozygous TT for SERPINB1 rs114597282. All genotype variants of SERPINB1 rs15286 were found in our Egyptian subjects with A being the minor allele. The SNP rs15286 was not found to be associated with risk of diabetes. The AA genotype was found to be associated with lower fasting plasma glucose, lower HbA1c%, and better ß-cell function and glycemic control in diabetic patients. The G allele was associated with poor glycemic control. Conclusions: The genotypes AA, AG, and GG of SERPINB1 gene SNP rs15286 are all represented in the studied sample; however, it is not associated with risk of diabetes. Genotype AA of SNP rs15286 is associated with better glycemic control and better ß-cell function in diabetic patients, while the G allele potentially represents the "risk allele" of poor glycemic control.