Abstract
Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS.Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders.Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12–1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48–0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (PI < 0.004–0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22–0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04–0.36) decreased the risk of IS (PI < 0.0001).Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.
Highlights
Blood lipid disorder is an important and modifiable risk factor for atherosclerosis [1, 2]
The average values of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, body mass index (BMI), and TG were higher in ischemic stroke (IS) than in control groups (P < 0.001 for all), whereas the percentages of subjects who consumed alcohol, the ApoA1/ApoB ratio, and the mean levels of TC, high-density lipoprotein cholesterol (HDL-C) and ApoA1 were lower in IS patients than in controls (P < 0.01 for all)
The major results of the present study are as follows: [1] Both genotype and allele frequencies of the rs11236530 single nucleotide polymorphisms (SNPs) were different between IS and control groups, the rs11236530CA/AA genotypes and A allele frequencies were higher in IS patients than in controls
Summary
Blood lipid disorder is an important and modifiable risk factor for atherosclerosis [1, 2]. Atherosclerosis, a progressive inflammatory disorder, is the most important cause of cardiovascular disease including ischemic stroke (IS), and its prevalence is high in middle-aged and elderly [3,4,5]. Both dyslipidemia and IS are common chronic diseases in which multiple genetic and environmental factors and their interaction are believed to involve the risk [6,7,8]. A recent genome-wide association study (GWAS) showed that heritability of IS was 37.9% [13], but it varied markedly by stroke subtype: large-vessel disease, 40.3%; cardio-embolic disease, 32.6%; and small-vessel disease, 16.1%. The present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
