Abstract
Objectives This study was to investigate the association of melatonin (MTN) pathway gene's single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE). Methods We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a (MTNR1a), MTNR1b, and arylalkylamine N-acetyltransferase (AANAT) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits. Results Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR = 0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR = 1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype. Conclusions The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE.
Highlights
Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease characterized by antinuclear autoantibody production and a multitude of immunecomplex deposition, which is involved in multisystem; such as the skin, kidney, and brain; and caused organs/tissue destruction [1, 2]
The normal controls consisted of age, gender, and ethnicity-matched healthy individuals who belonged to the same geographical area as that of cases; normal controls were excluded if they had a family history of SLE or any other autoimmune disease and history of any chronic or lifestyle diseases like depression, hypothyroidism, hypertension, diabetes mellitus, and tuberculosis (TB)
When analyzing the allele and genotype frequency of 3 tag single-nucleotide polymorphisms (SNPs) in arylalkylamine N-acetyltransferase (AANAT) genes, the results showed that two SNPs of rs8150 and rs3760138 were associated with the risk of SLE susceptibility, where CC carriers of rs8150 had a lower risk as compared to GG (OR = 0:537, 95% confidence intervals (CIs): 0.361, 0.799) (P = 0:002), whereas GG carrier of rs3760138 had an increased risk as compared to TT (OR = 1:823, 95% CI: 1.154, 2.880) (P = 0:010), but we did not observe other positive findings regarding the SNPs of rs12942767 (Table 3)
Summary
Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease characterized by antinuclear autoantibody production and a multitude of immunecomplex deposition, which is involved in multisystem; such as the skin, kidney, and brain; and caused organs/tissue destruction [1, 2]. In patients with SLE, a lower daily MTN level was observed as compared to healthy controls, and this decreased daily MTN level inversely correlated with the systemic lupus erythematosus disease activity index (SLEDAI) [19]. Study has revealed the seasonal pattern of MTN levels in SLE, with an elevated daily plasma MTN levels in December than in June [20].
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