Association of the genetic polymorphisms of the ACE gene and the eNOSgene with lupus nephropathy in northern Chinese population

Abstract

BackgroundIt has been reported that some single nucleotide polymorphisms (SNPs) of the angiotensin converting enzyme (ACE) gene and the endothelial nitric oxide synthase (eNOS) gene are associated with the development of systemic lupus erythematosus (SLE) and the progression of nephropathy. The aim of this study was to evaluate the possible association between six SNPs (A-5466C, T-3892C, A-240T, C1237T, G2215A and A2350G) of the ACE gene and two SNPs (T-786C and G894T) of the eNOS gene with lupus nephropathy in a northern Chinese population.MethodsIn this study, 225 patients with lupus nephropathy were compared to 232 healthy controls, matched by gender, age and ethnicity. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, the genotypes of the eight selected SNPs were determined by the method of PCR-RFLP; the haplotypes were inferred using PHASE 2.1. The associations between the SNPs and the risk of lupus nephropathy were analyzed using Chi-square test and Logistic regression with SPSS13.0 software.ResultsStatistically significant differences of the allele frequency distribution of three SNPs (A-5466C, A2350G and G894T) were observed between cases and controls (P < 0.05). Among the 53 haplotypes identified, the frequencies of five haplotypes (CTTCGA, ACTTAA, ACATGG, ACACGG and ATTCGA) were significantly different between cases and controls (P < 0.05).ConclusionsOur study indicated an association between the risk of lupus nephropathy and the sequence variations of both the ACE gene and the eNOS gene, which may play an important role in the pathogenesis of lupus nephropathy in the northern Chinese population. Further studies are warranted to validate our findings.

Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis

“…The eNOS polymorphisms have been associated with SLE by some authors, but by no means all [5][6][7][8][9][10][11][12], which may be due to small sample sizes, low statistical power, and/or clinical heterogeneity. Therefore, in order to overcome the limitations of individual studies, resolve inconsistencies, and reduce the likelihood that random errors are responsible for false-positive or false-negative associations, we turned to meta-analysis [13][14][15].…”

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

“…The lack of an association between the T-786C SNP and autoimmune diseases in the present study could be due to the predominance of the T allele within the Kuwaiti population. Table 4 shows data from different population studies in Kuwait [24], China [26,27], Columbia [28] and the USA [29] that also failed to find a significant association between the T-786C SNP and SLE, suggesting that it is unlikely to be a genetic susceptibility factor for SLE. Association of the T-786C SNP with HT has yet not been reported in any population study.…”

Angiotensin-converting enzyme insertion/deletion gene polymorphism is associated with dermatomyositis

“…29,30 Lupus nephritis is characterized by increasing vascular lesion risk, 13 and some studies have found that the ACE polymorphism was associated with lupus renal involvement. 10,14 In contrast to these diseases, there is no study thus far that has analyzed the ACE polymorphism in DM, a disease that involves vascular pathogenesis mediated by humoral processes with secondary ischemic changes of muscle fibers. 1,2,31,32 In these conditions, abnormalities have been found in the endothelium of capillaries, arterioles, and veins, which have been suggested to represent primary disease-related alterations.…”

“…[9][10][11][12][13][14] Nevertheless, to our knowledge, no studies to date have analyzed the ACE gene polymorphism in DM. Moreover, this polymorphism could be an attractive candidate among the factors that play a role in the development of vascular pathological and systemic inflammatory states; therefore, contributing to DM susceptibility and/or DM pathogenesis.…”