Endothelial Nitric Oxide Synthase Gene Polymorphisms Associated with Susceptibility to High Altitude Pulmonary Edema in Chinese Railway Construction Workers at Qinghai-Tibet over 4500 Meters above Sea Level

Objective To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level. Methods A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing. Results The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both P<0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both P<0.001). Conclusions Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.

Association of HLA-DR3 and HLA-DR15 Polymorphisms wi Risk of Systemic Lupus Erythematosus

Background:Systemic lupus erythematosus (SLE)is an autoimmune disease under genetic control.Growing evidences support the genetic predisposition ofHLA-DRB1 gene polymorphisms to SLE,yet the results are not often reproducible.The purpose of this study was to assess the association of two polymorphisms ofHLA-DRB1 gene (HLA-DR3and HLA-DR15)with the risk of SLE via a comprehensive meta-analysis. Methods:This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Case-control studies on HLA-DRB1 and SLE were searched from PubMed,Elsevier Science,Springer Link,Medline,and Cochrane Library database as of June 2018.Analysis was based on the random-effects model using STATA software version 14.0. Results:A total of 23studies were retained for analysis,including 5261cases and 9838controls.Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]:1.60,95%confidence interval (CI):1.316-1.934,P =0.129and OR:1.68,95%CI:1.334-2.112,P =0.001,respectively).Subgroup analyses demonstrated that for both HLA-DR3and HLA-DR15polymorphisms,ethnicity was a possible source of heterogeneity.Specifically,HLA-DR3polymorphism was not associated with SLE in White populations (OR:1.60,95%CI:1.320-1.960,P =0.522)and HLA-DR15polymorphism in East Asian populations (OR:1.65,95%CI:1.248-2.173,P =0.001).In addition,source of control was another possible source for both HLA-DR3and HLA-DR15polymorphisms,with observable significance for HLA-DR3in only population-based studies (OR:1.65,95% CI:1.370-1.990,P =0.244)and for HLA-DR15in both population-based and hospital-based studies (OR:1.38,95%CI:1.078-1.760, P =0.123and OR:2.08,95%CI:1.738-2.490,P =0.881,respectively). Conclusions:HLA-DRB1 gene may be a SLE-susceptibility gene,and it shows evident ethnic heterogeneity.Further prospective validations across multiple ethnical groups are warranted.