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Objective: Recent evidence from genetic, cell biology, and animal model studies has suggested a pivotal role of autophagy in mediating systemic lupus erythematosus (SLE). However, the genetic basis has not yet been thoroughly examined. Therefore, the aim of the present study was to identify additional susceptibility variants in autophagy‐related genes along with their functional significance. Methods: First, we performed a gene family–based genetic association analysis in SLE patients with the use of ImmunoChip arrays, and then we selected the most strongly associated polymorphisms for replication in additional cohorts. To identify regulatory clues, we analyzed publicly available blood expression quantitative trait locus data and Encyclopedia of DNA Elements data on transcription factor binding sites and cell type‐specific differential expression. Functional effects were tested by luciferase reporter assays, electrophoretic mobility shift assays, and differential gene expression assays. Results: In 14,474 samples, we observed that the rare Chinese variant rs933717T was associated with susceptibility to SLE (0.11% in cases versus 0.87% in controls; P = 2.36 × 10–10, odds ratio 0.13). The rs933717 risk allele C correlated with increased MAP1LC3B expression; increased MAP1LC3B messenger RNA was observed in SLE patients and in lupus‐prone mice. In reporter gene constructs, the risk allele increased luciferase activity up to 2.7‐3.8‐fold in both HEK 293T and Jurkat cell lines, and the binding of HEK 293T and Jurkat cell nuclear extracts to the risk allele was also increased. Conclusion: We observed a likely genetic association between light chain 3B, a widely used marker for autophagy, and susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Genome-wide association study recently identified the chromosome 3q22.3 as a novel locus associated with coronary artery disease (CAD). This study was designed to identify the critical haplotype blocks within this region in Han Chinese populations. Methods: We selected 1920 CAD patients and healthy participants from Han Chinese and genotyped 22 single nucleotide polymorphisms (SNPs) spanning 150 kilobases (kb) chromosomal region flanking rs9818870, a SNP associated with CAD at 3q22.3 in Caucasian. Results: Seven SNPs were found to be strongly associated with CAD in females and clustered in two haplotype blocks of ESYT3 gene. This was validated in two geographically isolated case-control populations. The two blocks were 14 and 25kb long, respectively. In a combined haplotype analysis, the odds ratios (95% confidence interval, permuted P value) were 0.70 (0.58–0.83, 2×10−5) and 1.44 (1.20–1.72, 5×10−5) for haplotypes TTG and CCA in block 1 as well as 0.73 (0.61–0.87, 3×10−4) and 1.35 (1.13–1.62, 0.0013) for haplotypes TCG and CTT in block 2, respectively. ESYT3 was expressed in human lymphocyte, vascular endothelial cell, and smooth muscle cell. The risk factors including gender, obesity, hypertension, diabetes, and hyperlipidemia exhibited strong effects on the genetic contribution to CAD. Conclusion: We identified two haplotype blocks of ESYT3 gene in 3q22.3 region that likely harbor functional variants, which cooperate with other risk factors and play a role in the pathogenesis of coronary artery disease in females. [Copyright &y& Elsevier]