Association Of Serum P-selectin Levels And P-selectin Gene Polymorphisms With Diabetic Nephropathy

Objective To investigate the association of serum P-selectin levels and polymorphisms of the C-2123G at promotor region of P-selectin gene with type 2 diabetic nephropathy in Qingdao Han population. Methods A case-control study on the 119 kinless Han nationality(including 75 type 2 diabetes mellitus and 44 normal control) in Qingdao region of China was performed. The type 2 diabetes mellitus patients were fractionated two subgroups according to urinary microalbumin excretion rate(UAER), including a normal albuminuria group (38 individulas) and a microalbuminuria group (37 individulas). serum P-selectin levels were measured by Enzyme-Linked Immunosorbnent Assay (ELISA) method. Fasting plasma glucose, fasting serum insulin,fasting serum C peptide, glycated haemoglobin (HbA1c), serum lipids concentrations, platelet parameters,and so on, were also measured at the same time in all subjects.Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) P-selectin -2123 genotypes were detected in above-mentioned 119 subjectes. Genotype frequencies and allele frequencies were calculated by direct counting. Finally to analysis the association of serum P-selectin levels and the three genotypes with the observed indexes. Results (1) The serum P-selectin levels in type 2 diabetes mellitus group and its two subgroups were higher than the normal control group(P<0.001). Serum P-selectin concentrations were also significantly increased in the microalbuminuria group compared with the normal albuminuria group. (2) Serum P-selectin levels correlated positively with mean platelet volume, urinary microalbumin excretion rate and fasting serum glucose in the microalbuminuria group. The concentrations of serum P-selectin in type 2 diabetes mellitus group had positive relationship to urinary microalbumin excretion rate and mean platelet volume. (3) The levels of serum P-selectin had linear regression relation to mean platelet volume, cholesterol and urinary microalbumin excretion rate in the microalbuminuria group.There also exist linear regression relation between serum P-selectin concentrations and these items(including mean platelet volume, cholesterol, urinary microalbumin excretion rate and platelet distribution width) in type 2 diabetes mellitus group. (4) There were two alleles (G,C) and three genotypes(GG,CC,CG)on the -2123 site at promotor region of P-selectin gene. The frequencies of the three genotypes and two alleles were not different in the two subgroups and normal control group(P>0.05). (5) The serum P-selectin levels of the three genotypes were different among the fractionated groups(P>0.05). The serum lipoprotein (a) concentrations of CG+CC' genotypes were significantly higher than GG genotype patients in type 2 diabetes mellitus group. Conclusions The serum P-selectin concentrations of the type 2 diabetes mellitus patients are higher than the normal individulas, and the concentrations are associated with the advancement of diabetic nephropathy. The examination of the serum P-selectin concentrations may be of some value to judge the genesis and advancement of diabetic nephropathy.The polymorphisms of the C-2123G at promotor region of P-selectin gene aren't concerned with diabetic nephropathy in Qingdao Han nationality, but the serum lipoprotein (a) concentrations of the CG+CC genotypes individuals are higher than the GG genotype population in this area.