Association of Melatonin Pathway Gene's Single-Nucleotide Polymorphisms with Systemic Lupus Erythematosus in a
Peng Wang1,2, Lei Liu3, Li-Fang Zhao2,4
1Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu, China.
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.
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