Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury

Abstract

Background: Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high density lipoprotein (HDL) which exerts innate protective effects in systemic inflammation. However, its role in the acute lung injury (ALI) has not been well studied. In the present study we investigated the association between polymorphisms of ApoA1 gene and ALI in a Chinese population.

Methods: Three polymorphisms of the ApoA1 gene (rs11216153, rs2070665, and rs632153) were genotyped by TaqMan method in 290 patients with sepsis-associated ALI, 285 patients sepsis alone and 330 age- and sex-matched healthy controls.

Results: We found rs11216153 polymorphism of ApoA1 was associated with ALI, the GG genotype and G allele was common in the ALI patients (76.9%, 88.1%, respectively) than both in the control subjects (55.8%, 75.8%, respectively) and in the sepsis alone patients (58.2%, 78.4%, respectively). Haplotype consisting of these three SNPs strengthened the association with ALI susceptibility. The frequency of haplotype GTG in the ALI samples was significantly higher than that in the healthy control group (OR = 2.261, 95% CI: 1.735 ~ 2.946, P <0.001) and the sepsis alone group (OR = 1.789, 95% CI: 1.373 ~ 2.331.P < 0.001). Carriers of the haplotype TTG had a lower risk for ALI compared with healthy control group (OR = 0.422, 95% CI: 0.310 ~ 0.574, P < 0.001) and sepsis alone group (OR = 0.491, 95% CI: 0.356 ~ 0.676, P <0.001).

Conclusions: These results indicated that genetic variants in the ApoA1 gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population.

Figure 1

Genetic variation at human ApoA1 gene. Using the Haploview 4.2 software and the HapMap phrase II database, we scanned 5 genotyped single-nucleotide polymorphisms (SNPs) in Chinese Han. Linkage disequilibrium (LD) blocks across the locus in Chinese Han. LD block derived by solid spline method in Haploview 4.2. LD value shown: (A) |D’| × 100; |D’| colour scheme: |D’| =0: white; 0 < |D’| < 1: shades of pink; |D’| =1: red; (B) r ² × 100; r ² colour scheme: r ² = 0: white; 0 < r 2 < 1: shades of grey; r ² = 1: black.