Apolipoprotein-E Gene Polymorphism and Lipid Composition among IUGR and AGA Neonates

Abstract

Objective The objective of this study is to study the profile of apolipoprotein E (APOE) gene polymorphism and lipid profile among intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) neonates. This is an observational study. This study was done at the neonatal unit of a teaching hospital in South India. All consecutively born IUGR neonates (cases) of more than 32 weeks' gestational age and AGA neonates (controls) were enrolled for the study. Genomic DNA extraction was done from a total of 102 peripheral venous blood samples. Genotyping of the APOE rs429358 and rs7412 defining the ε2, ε3, and ε4 alleles was done by polymerase chain reaction–restriction fragment length polymorphism method. Prefeed venous blood was collected and analyzed for lipid profile estimation. The allelic frequencies of cases versus control were ε2—9 (8.7%) versus 3 (2.9%); ε3—88 (84.6%) versus 81 (79.4%); and ε4–7 (6.7%) versus 18 (17.6%). The frequency of ε4 isoform allele, associated with adult onset of metabolic diseases was less among the IUGR group. The mean total cholesterol (TC), Low-Density Lipoprotein (LDL), High-Density Lipoprotein, and triglyceride (TG) were 107.59 ± 35.99, 51.69 ± 24.68, 21.75 ± 9.58, and 151.22 ± 61.84 mg/dL, respectively, in the IUGR group. The mean TC and LDL levels in IUGR group were marginally higher than AGA neonates (107 ± 35.99 vs. 100.37 ± 22.69 mg/dL and 51.69 ± 24.68 versus 46.9 ± 19.51 mg/dL, p > 0.05). In both groups, the mean TC and TGL levels were elevated in the ε4 isoform subgroup (p > 0.05). In our study, the ε2 allele was the second most predominant APOE isoform and the ε4 allele of the APOE gene associated with adult-onset diseases was not increased among IUGR neonates. Neonates with ε4 allele showed an abnormal lipid profile in both study groups suggesting a possible association.

Keywords

intrauterine growth restriction neonates - apolipoprotein E gene polymorphism - lipid profile

Publikationsverlauf

Eingereicht: 09. September 2020

Angenommen: 16. November 2020

Artikel online veröffentlicht:
11. Februar 2021

• References

• 1 Sharma D, Shastri S, Farahbakhsh N, Sharma P. Intrauterine growth restriction – Part 1. J Matern Fetal Neonatal Med 2016; 7: 1-11
• 2 de Onis M, Blössner M, Villar J. Levels and patterns of intrauterine growth retardation in developing countries. Eur J Clin Nutr 1998; 52 (Suppl. 01) S5-S15
• 3 Sharma D, Farahbakhsh N, Shastri S, Sharma P. Intrauterine growth restriction - Part 2. J Matern Fetal Neonatal Med 2016; 29 (24) 4037-4048
• 4 Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”?. Am J Hum Genet 1962; 14: 353-362
• 5 Longo S, Bollani L, Decembrino L, Di Comite A, Angelini M, Stronati M. Short-term and long-term sequelae in intrauterine growth retardation (IUGR). J Matern Fetal Neonatal Med 2013; 26 (03) 222-225
• 6 Menendez-Castro C, Cordasic N, Schmid M. et al. Intrauterine growth restriction promotes vascular remodelling following carotid artery ligation in rats. Clin Sci (Lond) 2012; 123 (07) 437-444
• 7 Mahley RW, Rall Jr SC. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000; 1: 507-537
• 8 Utermann G, Hees M, Steinmetz A. Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature 1977; 269 (5629): 604-607
• 9 Bennet AM, Di Angelantonio E, Ye Z. et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007; 298 (11) 1300-1311
• 10 Davignon J, Cohn JS, Mabile L, Bernier L. Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta 1999; 286 (1-2): 115-143
• 11 Moghadasian MH, McManus BM, Nguyen LB. et al. Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. FASEB J 2001; 15 (14) 2623-2630
• 12 Stannard AK, Riddell DR, Sacre SM. et al. Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J Biol Chem 2001; 276 (49) 46011-46016
• 13 Dallongeville J, Lussier-Cacan S, Davignon J. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res 1992; 33 (04) 447-454
• 14 Infante-Rivard C, Lévy E, Rivard GE, Guiguet M, Feoli-Fonseca JC. Small babies receive the cardiovascular protective apolipoprotein epsilon 2 allele less frequently than expected. J Med Genet 2003; 40 (08) 626-629
• 15 Barker DJ. In utero programming of chronic disease. Clin Sci (Lond) 1998; 95 (02) 115-128
• 16 de Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust N Z J Obstet Gynaecol 2006; 46 (01) 4-14
• 17 Dötsch J. Perinatal programming - myths, fact, and future of research. Mol Cell Pediatr 2014; 1 (01) 2
• 18 Hales CN. Fetal and infant growth and impaired glucose tolerance in adulthood: the “thrifty phenotype” hypothesis revisited. Acta Paediatr Suppl 1997; 422: 73-77
• 19 Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ. Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001; 322 (7292): 949-953
• 20 Levitt NS, Lambert EV, Woods D, Hales CN, Andrew R, Seckl JR. Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: early programming of cortisol axis. J Clin Endocrinol Metab 2000; 85 (12) 4611-4618
• 21 Crispi F, Bijnens B, Figueras F. et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation 2010; 121 (22) 2427-2436
• 22 Beisiegel U, Weber W, Ihrke G, Herz J, Stanley KK. The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein. Nature 1989; 341 (6238): 162-164
• 23 Mastana SS, Calderon R, Pena J, Reddy PH, Papiha SS. Anthropology of the apoplipoprotein E (apo E) gene: low frequency of apo E4 allele in Basques and in tribal (Baiga) populations of India. Ann Hum Biol 1998; 25 (02) 137-143
• 24 Corbo RM, Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?. Ann Hum Genet 1999; 63 (Pt 4): 301-310
• 25 Singh P, Singh M, Gerdes U, Mastana SS. Apolipoprotein E polymorphism in India: high APOE*E3 allele frequency in Ramgarhia of Punjab. Anthropol Anz 2001; 59 (01) 27-34
• 26 Weisgraber KH, Innerarity TL, Mahley RW. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem 1982; 257 (05) 2518-2521
• 27 Akisu M, Balim Z, Cetin H. et al. The role of angiotensin-converting enzyme and apolipoprotein-E gene polymorphisms on lipid compositions in newborn infants with intrauterine growth restriction. Early Hum Dev 2004; 78 (02) 95-103
• 28 Norda S, Rausch TK, Orlikowsky T. et al. Apolipoprotein E genotype in very preterm neonates with intrauterine growth restriction: an analysis of the German Neonatal Network cohort. BioMed Res Int 2017; 2017: 2837027
• 29 Guang-da X, You-ying L, Zhi-song C, Yu-sheng H, Xiang-jiu Y. Apolipoprotein e4 allele is predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus. Atherosclerosis 2004; 175 (01) 77-81
• 30 Kumar P, Luthra K, Dwivedi M, Behl VK, Pandey RM, Misra A. Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India. Ann Clin Biochem 2003; 40 (Pt 4): 382-387
• 31 van Bockxmeer FM, Mamotte CD. Apolipoprotein epsilon 4 homozygosity in young men with coronary heart disease. Lancet 1992; 340 (8824): 879-880
• 32 Kuusi T, Nieminen MS, Ehnholm C. et al. Apoprotein E polymorphism and coronary artery disease. Increased prevalence of apolipoprotein E-4 in angiographically verified coronary patients. Arteriosclerosis 1989; 9 (02) 237-241
• 33 Chaudhary R, Likidlilid A, Peerapatdit T. et al. Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc Diabetol 2012; 11: 36