Association Study Of Midkine And Pleiotrophin Gene Single Nucleotide Polymorphisms With Susceptibility To Systemic Lupus Erythematosus

ObjectiveRecently,several studies have revealed that midkine(MK)and pleiotrophin(PTN)play an important role in multiple autoimmune diseases.In our previous study,we have reported an elevated plasma MK and PTN concentrations in systemic lupus erythematosus(SLE)patients,and it was associated with inflammatory cytokines IL-17 level and some clinical manifestations,suggesting a potential role of MK and PTN in the pathogenesis of SLE.In the present study,we aimed to investigate the association of MK and PTN gene single nucleotide polymorphisms(SNPs)with SLE susceptibility in a Chinese Han population.MethodsThis case–control genotyping study comprised a total of 989 subjects.Four hundred and ninety-six patients with SLE were recruited from the Department of Rheumatology and Immunology at Anhui Provincial Hospital,the First Affiliated Hospital of Anhui Medical University.The diagnosis of SLE was established according to the 1997 revised American College of Rheumatology(ACR)classification criteria.Four hundred and ninety-three geographically and ethnically matched healthy controls were enrolled in the current study.All the healthy controls were recruited from Physical Examination Center of the First Affiliated Hospital of Anhui Medical University and the Second Affiliated Hospital of Anhui Medical University.Improved multiple ligase detection reaction(iMLDR)was utilized to genotype the SNPs,which including three MK SNPs(rs116869512,rs20542 and rs35324223)and seven PTN SNPs(rs161335,rs321198,rs322236,rs3959914,rs6970141,rs919581 and rs322297).Enzyme-linked immuno sorbent assay was used to detect the serum MK and PTN expression.ResultsThis study included a total of 989 subjects(496 patients with SLE,493 healthy controls).Among 496 SLE patients,there were 438 females(88.30%)and 58 males(11.70%)with an average age of 37.58±11.44 years;while in 493 healthy controls,there were 434 females(88.00%)and 59 males(12.00%)with an average age of38.45±11.32 years.There was no significant difference in genotype and allele frequencies in all 10 SNPs between SLE patients and healthy controls(all P>0.05).When analyzing the recessive,dominant and additive models of genotype effects,no evidence showed an association between 10 SNPs with SLE susceptibility(all P>0.05).Case-only analysis indicated that,in MK gene,the frequency of AA/AG genotype(rs35324223)polymorphism was significantly lower in patients with photosensitivity than in those without(?~2=7.332,P=0.012),the allelic frequency of A/G(rs20542)was significantly higher in patients without serositis(?~2=4.291,P=0.042).In PTN,the A/G allele frequencies(rs322236)and C/T allele frequencies(rs6970141)polymorphism demonstrated a significantly increased result in patients with immunological disorder compared to those without(?~2=5.670,P=0.020;?~2=4.962,P=0.027,respectively).Four main haplotypes(AAA,CAA,CGA and CGG)for MK gene and eight main haplotypes(CCATCTA,CCATTTG,CTATCTA,CTATTTA,CTATTTG,TCATCTA,TCATTTA and TCATTTG)for PTN gene were identified by using SHEsis software.However,no significant differences of MK and PTN gene haplotypes were found(all P>0.05).In addition,there were no significant differences in serum MK and PTN concentrations with its SNPs genotypes.ConclusionsOverall,MK and PTN SNPs showed no association with SLE genetic susceptibility,but may contribute to some clinical and laboratory parameters of this disease;functional studies are needed to explore the mechanism of MK and PTN genes in the pathogenesis of SLE.