The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang

Abstract

BackgroundThe present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China.MethodsFour hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes. Their mutation difference was analyzed by SNaP shot techniques. GeneMapper4.1 SPSS20.0 software was used for data management and analysis. Using a single locus analysis, the distribution difference of genotype loci in ischemic stroke cases and controls were detected to assess the genetic risk factors of ischemic stroke.ResultsSignificance differences of genotype distribution in ischemic stroke cases and controls were observed in LDLR rs688 in Han and Uighur population in recessive model from analysis of single gene locus. It also was found that dramatic difference of triglyceride (TG) of LPL rs328 and systolic blood pressure in CETP rs708277 of total population. In binary logistic regression analysis of total studied population, ischemic stroke was observed significantly associated with LDLR rs688 both addictive model (TT/CC, adjusted OR = 1.47, 95% CI = 1.04–2.07) and recessive model (TT/CT + CC, adjusted Odds ratio (OR) = 2.66, 95% Confidence Interval (CI) = 1.37–5.14). In Han population, ischemic stroke was observed significantly associated with rs688 both in addictive model (TT/CC, adjusted OR = 3.27, 95% CI = 1.06–10.05). In Uighur population, no significant association was found between gene polymorphisms and the risk of ischemic stroke. Combined analysis of multiple gene and loci, interaction effects of LDLR rs688 C/T, ApoA5 rs662799 A/G and CETP rs708272 C/T denoted a significant influence on IS susceptibility.ConclusionSingle nucleotide polymorphisms of lipid metabolism relative gene were significantly associated with the morbidity of ischemic stroke in Han population. The interaction effects of rs688 C/T with ApoA5 rs662799 A/G and CETP rs708272 C/T promoted the occurrence of IS.

The HindIII and PvuII polymorphisms of lipoprotein lipase (LPL) gene reduce the risk of ischemic stroke (IS)

“…[48] Huang et al [27] firstly investigated the genetic association between HindIII (+/−) variant and stroke, and obtained negative results. This result was followed by Song et al, [30] Velásquez Pereira et al, [22] and Xu et al [28] Although negative results were observed in individual study, our study confirmed this variant in allelic and dominant models were associated with a significant reduction of the IS risk especially in Asian population, which was similar with the results reported in latest publication by He et al [51] Notable, we included 2 more studies [30,37] and found that the recessive model of HindIII (+/−) might not be the susceptible factor of IS, which was partly different from that reported by He et al [51] In addition, we excluded 3 studies [52–54] that included in study conducted by He et al on the association between the HindIII (+/−) and hemorrhagic stroke (HS) risk for the present meta-analysis mainly focused on the association between HindIII (+/−) and IS risk. Recent studies suggested that HS and IS were 2 different subtype of stroke.…”

“…[23,28] Four articles reported the association between 2 LPL polymorphisms and IS. [22,27,30,37] For there were 2 different populations in the study conducted by Yue et al, [37] we treated each group as an individual studies. Finally, a total of 19 studies were enrolled in present study.…”

“…[22–24,28,37–45] Ten studies with 2109 cases and 2081 controls were included for LPL for HindIII (+/−). [22,23,25–28,30,37,46] And 6 studies with 786 cases and 896 controls were included for LPL PvuII (+/−). [22,23,27–30] The studies involved and their main characteristics were shown in Table 1.…”

The association between polymorphism of LDL-R gene and ischemic stroke risk in Chinese population: A meta-analysis

“…As a functional variant, rs688 can modulate LDL-R splicing efficiency [ 35 ], and has been associated with CAD [ 36 , 37 ]. Previous studies [ [24] , [25] , [26] ] showed that T allele of LDL-R rs688 gene was significantly associated with susceptibility of ischemic stroke. In contrast, some other studies [ 21 , 35 ] demonstrated LDL-R rs688 polymorphism were lack of significance of risk of ischemic stroke.…”

“…Based on these findings, we hypothesized that polymorphisms of rs1122608 and rs688 in the LDL-R locus play a role in the development of stroke and are relevant to the risk of ischemic stroke in the Chinese population. However, with the premise of inconsistent results from previous studies, several studies have focused on the association between LDL-R gene polymorphism and ischemic stroke risk recently [ [21] , [22] , [23] , [24] , [25] , [26] , [27] ]. Li et al found that T allele of LDL-R rs688 gene was significantly associated with susceptibility of ischemic stroke [ 24 ], unlike this, other studies suggested LDL-R rs688 variant were lack of significance of risk of ischemic stroke by Lee et al [ 27 ] and Wang et al [ 21 ].…”