India is undergoing an epidemiological transition and an alarming rise in the prevalence of coronary artery disease (CAD). The etiopathology of the disease is evolving to a more complex setting with the discovery of novel risk factors. In the quest for non-traditional risk factors, we found that Lipoprotein(a) gene and its product are unique and pertinent to the Indian population. To unravel the genetic blueprint of the variations within the LPA gene in Indians, we studied novel exonic and intronic SNPs in 60 patients with angiographically proven CAD and matched them with healthy volunteers. From the study, we observed that in our patients, LPA aspirin genotype rs3798220 did not cause variation in Lp(a) levels in either of the two groups which is a novel finding as it is at odds with most published studies from other populations, on this variant. The polymorphic allele of SNP rs1321196 increased serum Lp(a) levels but the presence of the variant was however not limited to the patient population. The SNP rs9364564 did not influence Lp(a) levels in either of the two groups of the study. The study is unique as it bears witness to the novelty of the genotype background in Indian patients with CAD.
Krishnan MN. Coronary heart disease and risk factors in India – On the brink of an epidemic? Indian Heart J 2012;64(4):364–367. DOI: 10.1016/j.ihj.2012.07.001.
India State-Level Disease Burden Initiative CVD Collaborators. The changing patterns of cardiovascular diseases and their risk factors in the states of India: the global burden of disease study 1990–2016. Lancet Glob Health 2018;6(12):e1339–e1351. DOI: 10.1016/S2214-109X(18)30407-8.
Abdul-Aziz AA, Desikan P, Prabhakaran D, et al. Tackling the burden of cardiovascular diseases in India. Circ Cardiovasc Qual Outcomes 2019;12(4):e005195. DOI: 10.1161/CIRCOUTCOMES.118.005195.
Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009;361(26):2518–2528. DOI: 10.1056/NEJMoa0902604.
Jayasinghe R, Craig IH, Mohan RK. Lipoprotein (A) in clinical practice. J Pak Med Assoc 2014;64(4):447–450.
Zlatohlávek L, Zídková K, Vrablík M, et al. Lipoprotein (a) and its position among other risk factors of atherosclerosis. Physiol Res 2008;57(5):777–783. DOI: 10.33549/physiolres.931133.
Enas EA, Chacko V, Senthilkumar A, et al. Elevated lipoprotein(a)–a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis Mon 2006;52(1):5–50. DOI: 10.1016/j.disamonth.2006.01.002.
Gabel BR, Koschinsky ML. Sequences within apolipoprotein(a) kringle IV types 6-8 bind directly to low-density lipoprotein and mediate noncovalent association of apolipoprotein(a) with apolipoprotein B-100. Biochemistry 1998;37(21):7892–7898.
Gabel BR, Koschinsky MI. Analysis of the proteolytic activity of a recombinant form of apolipoprotein(a). Biochemistry 1995;34(48):15777–15784. DOI: 10.1021/bi00048a023.
Schmidt K, Noureen A, Kronenberg F, et al. Structure, function, and genetics of lipoprotein (a). J Lipid Res 2016;57(8):1339–1359. DOI: 10.1194/jlr.R067314.
Scanu AM. Lp(a) lipoprotein--coping with heterogeneity. N Engl J Med 2003;349(22):2089–2090. DOI: 10.1056/NEJMp038128.
Hoek YY, Wittekoek ME, Wittekoek ME, et al. The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variably-sized isoforms. Hum Mol Genet 1993;2(4):361–366. DOI: 10.1093/hmg/2.4.361.
Ashfaq F, Goel P, Ali W, et al. Lipoprotein (a) levels in relation to severity of coronary artery disease in North Indian patients. Heart Views 2013;14(1):12–16. DOI: 10.4103/1995-705X.107114.
Frank S, Klisak I, Sparkes R, et al. The apolipoprotein(a) gene resides on human chromosome 6q26-27, in close proximity to the homologous gene for plasminogen. Hum Genet 1988;79(4):352–356. DOI: 10.1007/BF00282175.
Maranhão RC, Carvalho PO, Strunz CC, et al. Lipoprotein (a): structure, pathophysiology and clinical implications. Arq Bras Cardiol 2014;103(1):76–84. DOI: 10.5935/abc.20140101.
Dumitrescu L, Glenn K, Brown-Gentry K, et al. Variation in LPA is associated with Lp(a) levels in three populations from the third national health and nutrition examination survey. PLoS One 2011;6(1):e16604. DOI: 10.1371/journal.pone.0016604.
Barlera S, Specchia C, Farrall M, et al. Multiple QTL influence the serum Lp(a) concentration: a genome-wide linkage screen in the PROCARDIS study. Eur J Hum Genet 2007;15(2):221–227. DOI: 10.1038/sj.ejhg.5201732.
Broeckel U, Hengstenberg C, Mayer B, et al. A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 2002;30(2):210–214. DOI: 10.1038/ng827.
Burman A, Jain K, Gulati R, et al. Lipoprotein(a) as a marker of coronary artery disease and its association with dietary fat. J Assoc Physicians India 2004;52:99–102.
Perez-Guzman C, Vargas MH. Hypocholesterolemia: a major risk factor for developing pulmonary tuberculosis? Med Hypotheses 2006;66(6):1227–1230. DOI: 10.1016/j.mehy.2005.12.041.
Moutzouri E, Elisaf M, Liberopoulos E. Hypocholesterolemia. Curr Vasc Pharmacol 2011;9(2):200–212. DOI: 10.2174/157016111794519354.
Vandana S, Bhatnagar MK, Jayashree B. Evaluation of homocysteine, lipoprotein(a) and endothelin as diagnostic markers of coronary artery disease in Indian population. Internet J Med Update 2013;8(1):17–23.
Deo RC, Wilson JG, Xing C, et al. Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans. PLoS One 2011;6(1):e14581. DOI: 10.1371/journal.pone.0014581.
Arai K, Luke MM, Koschinsky ML, et al. The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles. Atherosclerosis 2010;209(2):498–503. DOI: 10.1016/j.atherosclerosis.2009.09.077.
Shiffman D, Kane JP, Louie JZ, et al. Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction. PLoS One 2008;3(8):e2895. DOI: 10.1371/journal.pone.0002895.
Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis 2009;203(2):371–376.
Khalifa M, Noureen A, Ertelthalner K, et al. Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians. Atherosclerosis 2015;242(2):521–528.