Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population

Abstract

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

Effect modification by region in the associations ofLEP G2548AandLEPR Q223Rpolymorphisms with statin-induced CK elevation

“…We did not measure leptin levels, so we could not determine whether the LEP and LEPR polymorphisms were associated with leptin levels or whether the LEP and LEPR polymorphisms and leptin levels interacted in their associations with the outcomes in this study. Limited evidence showed that neither LEP G2548A nor LEPR Q223R polymorphisms were significantly associated with plasma leptin levels in Chinese populations [ 51 , 52 ]. Therefore, we are considering to measure serum leptin, adipokine and soluble leptin receptor concentrations in our ongoing large scale cardiovascular cohort project.…”

Metabolic determinants of lupus pathogenesis

“…However, SLE patients with reduced serum leptin have also been reported in some studies, while others show no difference between SLE patients and HCs . Genetic variations in the leptin and leptin receptor genes are associated with some clinical parameters of SLE such as photosensitivity and pericarditis, in spite of a lack of association with genetic susceptibility to SLE . High leptin levels in SLE patients correlate with vascular stiffness parameters, increased risk for atherosclerosis, and with increased inflammatory atherosclerotic biomarkers .…”

“…90 Genetic variations in the leptin and leptin receptor genes are associated with some clinical parameters of SLE such as photosensitivity and pericarditis, in spite of a lack of association with genetic susceptibility to SLE. 91 High leptin levels in SLE patients correlate with vascular stiffness parameters, increased risk for atherosclerosis, and with increased inflammatory atherosclerotic biomarkers. 92,93 Furthermore, high levels of circulating leptin correlate with subclinical atherosclerosis in SLE patients with MetS.…”

Leptin and systemic lupus erythematosus: A comprehensive review

“…There are increasing evidence of the involvement of leptin in maintenance of the immune system [46]. Leptin may stimulate activation and proliferation of peripheral blood mononuclear cells (PBMCs) through its receptors which are expressed on these cells.…”