Skip to main content
Log in

Case–Control Study and Meta-Analysis of the Association Between LIPG rs9958947 SNP and Stroke Risk

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The rs9958947 single nucleotide polymorphism (SNP) resides in the promoter region of the lipase G (LIPG) gene. This newly discovered SNP increases the risk of stroke in some Asian populations, including Chinese and Korean populations. Stroke is one of the top 5 leading causes of death in Malaysia, so it is of interest to investigate whether this SNP is associated with stroke risk in the Malaysian population. Therefore, this study investigates this association through a case–control study on a Malaysian population along with a comprehensive meta-analysis. Genotyping of LIPG rs9958947 SNP was performed for 241 Malaysians using real-time polymerase chain reaction, and the odds ratios (OR) with 95% confidence intervals were calculated. The meta-analysis was conducted using the software Comprehensive Meta-Analysis ver. 2.2.064. A p value less than 0.05 was considered statistically significant. We observed that the mean age of Malaysian stroke patients was less than that of stroke patients from Korea and China. The meta-analysis showed that the LIPG rs9958947 SNP was significantly associated with an increased risk of ischemic stroke in Asian populations (dominant (CC vs. CT + TT): OR = 1.45, p < 0.001; allelic (C vs. T): OR = 1.21, p = 0.001; heterozygous (CC vs. CT): OR = 1.47, p < 0.001, and homozygous (CC vs. TT): OR = 1.46, p = 0.047). However, there was no evidence to associate this SNP with stroke risk in the Malaysian population (overall CC vs. CT: OR = 1.04, CC vs. TT: OR = 1.25, CC vs. CT + TT, OR = 1.13; all p > 0.05) and blood lipid levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

The datasets analyzed in this study are available from the corresponding author on request.

References

  • Begg CB, Majumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  Google Scholar 

  • Centres for Disease Control and Prevention (2017) Types of stroke. CDC Press, Georgia

    Google Scholar 

  • Cheah WK, Hor CP, Aziz ZA, Looi I (2016) A review of stroke research in Malaysia from 2000–2014. Med J Malaysia 71:58–69

    CAS  PubMed  Google Scholar 

  • Department of Statistics Malaysia (2019) Statistics on causes of death, Malaysia, 2019. Department of Statistics Malaysia Press, Putrajaya

    Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  Google Scholar 

  • Du HQ, Shen X, Mou YF, Dong LG, Li PG, Sun YY, Zuo CX, Hou YC, Shi Q (2013) Relationship between LIPG gene promoter polymorphism and lacunar infarction. J Navy Med 3:150–154

    Google Scholar 

  • Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demssie S, Manning AK, Jensen MK, Rimm EB, Wang J, Rodrigues A et al (2009) Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J Clin Invest 119:1042–1050

    CAS  PubMed  PubMed Central  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629

    Article  CAS  Google Scholar 

  • Ellison RC, Zhang Y, Qureshi MM, Knox S, Arnett DK, Province MA, Investigators of the NHLBI Family Heart Study (2004) Lifestyle determinants of high-density lipoprotein cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J 147:529–535

    Article  CAS  Google Scholar 

  • Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson L, Truelsen T et al (2014) Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 383:245–254

    Article  Google Scholar 

  • Feigin VL, Krishnamurthi RV, Parmar P, Norrving B, Mensah GA, Bennett DA, Barker-Collo S, Moran AE, Sacco RL, Truelsen T et al (2015) Update on the global burden of ischemic and hemorrhagic stroke in 1990–2013: the GBD 2013 study. Neuroepidemiology 45:161–176

    Article  Google Scholar 

  • Halverstadt A, Phares DA, Wilund KR, Goldberg AP, Hagberg JM (2007) Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women. Metabolism 56:444–450

    Article  CAS  Google Scholar 

  • Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  Google Scholar 

  • Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557

    Article  Google Scholar 

  • Ishida T, Choi S, Kundu RK, Hirata K, Rubin ED, Cooper AD, Quertermous T (2003) Endothelial lipase is a major determinant of HDL level. J Clin Invest 111:347–355

    Article  CAS  Google Scholar 

  • Jaye M, Lynch KJ, Krawiec J, Marchadier D, Maugeais C, Doan K, South V, Amin D, Perrone M, Rader DJ (1999) A novel endothelial-derived lipase that modulates HDL metabolism. Nature Genet 21:424–428

    Article  CAS  Google Scholar 

  • Jensen MK, Rimm EB, Mukamal KJ, Edmondson AC, Rader DJ, Vogel U, Tjønneland A, Sørensen TIA, Schmidt EB, Overvad K, (2009) The T111I variant in the endothelial lipase gene and risk of coronary heart disease in three independent populations. Eur Heart J 30:1584–1589

    Article  CAS  Google Scholar 

  • Jin W, Sun GS, Marchadier D, Octtaviani E, Glick JM, Rader DJ (2003) Endothelial cells secrete triglyceride lipase and phospholipase activities in response to cytokines as a result of endothelial lipase. Circ Res 92:644–650

    Article  CAS  Google Scholar 

  • Kelly-Hayes M (2010) Influence of age and health behaviors on stroke risk: lessons from longitudinal studies. J Am Geriatr Soc 58:S325–S328

    Article  Google Scholar 

  • Kim NS, Ko MM, Cha MH, Bang OS (2012) LIPG promoter polymorphism is associated with ischemic stroke in Korean population. Genes Genom 34:165–171

    Article  CAS  Google Scholar 

  • Linsel-Nitsehke P, Tall AR (2005) HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov 4:193–205

    Article  Google Scholar 

  • Ma L, Yang J, Runesha HB, Tanaka T, Ferrucci L, Bandinelli S, Da Y (2010) Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data. BMC Med Genet 11:55

    Article  CAS  Google Scholar 

  • Mank-Seymour AR, Durham KL, Thompson JF, Seymour AB, Milos PM (2004) Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels. Biochim Biophys Acta 1636:40–46

    Article  CAS  Google Scholar 

  • Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    CAS  PubMed  Google Scholar 

  • Mozzafarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després J, Fullerton HJ et al (2016) Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 133:e38–e360

    Google Scholar 

  • Otokozawa S, Ai M, Asztalos BF, White CC, Demissie-Banjaw S, Cupples LA, Nakajima K, Wilson PWF, Schaefer EJ (2010) Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: Results from the Framingham Offspring Study. Atherosclerosis 213:251–255

    Article  CAS  Google Scholar 

  • Phneh KY, Chong ETJ, Sybil Shah S, Chia YK, Ag. Daud DM, Jalil E, Cheng KCS, Lee PC, (2019) A case-control study and meta-analysis of the association of eNOS rs1799983 SNP with stroke risk. Med Health 14:118–134

    Article  CAS  Google Scholar 

  • Schmidt MD, Cleland VJ, Thomson RJ, Dwyer T, Venn AJ (2008) A comparison of subjective and objective measures of physical activity and fitness in identifying associations with cardiometabolic risk factors. Ann Epidemiol 18:378–386

    Article  Google Scholar 

  • Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, Fornage M, Ikram MA, Malik R, Bevan S et al (2012) Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome wide association studies. Lancet Neurol 11:951–962

    Article  Google Scholar 

  • Venketasubramanian N, Tan LCS, Sahadevan S, Chin JJ, Krishnamoorthy ES, Hong CY, Saw SM (2005) Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: a community-based tri-racial cross-sectional survey. Stroke 36:551–556

    Article  Google Scholar 

  • Vergeer M, Cohn DM, Boekholdt SM, Sandhu MS, Prins HM, Ricketts SL, Wareham NJ, Kastelein JJP, Khaw KT, Kamphuisen PW et al (2010) Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT. Atherosclerosis 211:558–564

    Article  CAS  Google Scholar 

  • Wang J, Zheng B, Wang QS, Wang J, Cheng SY, Li J (2014) Association of endothelial lipase genetic polymorphism with lacunar infarction in a Chinese population. Int J Clin Exp Med 7:4427–4433

    PubMed  PubMed Central  Google Scholar 

  • Wilier CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM et al (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nature Genet 40:161–169

    Article  Google Scholar 

  • Yu JE, Han SY, Wolfson B, Zhou Q (2018) The role of endothelial lipase in lipid metabolism, inflammation, and cancer. Histol Histopathol 33:1–10

    PubMed  Google Scholar 

  • Zeljkovic A, Vekic J, Spasojevic-Kalimanovska V, Jelic-Ivanovic Z, Bogavac-Stanojevic N, Gulan B, Spasic S (2010) LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality. Atherosclerosis 210:548–554

    Article  CAS  Google Scholar 

Download references

Funding

This study is financially supported by the Ministry of Higher Education, Malaysia (TRGS0006-SG-2/2014) and Universiti Malaysia Sabah (GUG0128-1/2017).

Author information

Authors and Affiliations

Authors

Contributions

PCL and ETJC conceived and designed the study. KYP, ETJC, SSS, YKC, DMAD, EJ, CSKC, and PCL collected the data. KYP and ETJC conducted the experiments, analyzed the data, and drafted the manuscript. PCL revised the final version of the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Ping-Chin Lee.

Ethics declarations

Competing Interests

The authors declare that there is no conflict of interest.

Ethics Approval

This study was approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia with reference no: NMRR-16–38-28777 (IIR). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Phneh, K.Y., Chong, E.T.J., Shah, S.S. et al. Case–Control Study and Meta-Analysis of the Association Between LIPG rs9958947 SNP and Stroke Risk. J Mol Neurosci 71, 2085–2094 (2021). https://doi.org/10.1007/s12031-021-01795-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-021-01795-w

Keywords

Navigation