Systematic Review and Meta-analysis: Gene Association Studies in Neonatal Sepsis

Lakshmi Srinivasan; Daniel T. Swarr; Megha Sharma; C. Michael Cotten; Haresh Kirpalani

doi:10.1055/s-0036-1597132

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2017; 34(07): 684-692
DOI: 10.1055/s-0036-1597132

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systematic Review and Meta-analysis: Gene Association Studies in Neonatal Sepsis

Lakshmi Srinivasan

¹Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

,

Daniel T. Swarr

¹Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

,

Megha Sharma

²Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin

,

C. Michael Cotten

³Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina

,

Haresh Kirpalani

¹Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

› Institutsangaben

Abstract

Background Association studies of various gene variants in neonatal sepsis show conflicting results.

Objective We performed a systematic review of candidate gene association studies in neonatal sepsis to provide pooled estimates of risk for selected gene variants.

Methods We performed a search using MeSH terms “infection,” “sepsis,” “infant,” “genetic variation,” “polymorphism,” and “genetic association studies.” We included studies evaluating associations between neonatal sepsis and genetic variants (2000–2015). We excluded case reports/series, commentaries, narrative reviews, and nonhuman research. We assessed quality of studies using STREGA guidelines. Following estimation of odds ratios (ORs), data were pooled using random effects models.

Results Twenty eight of 1,404 identified studies were included. Meta-analyses were performed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 as these gene variants were tested in multiple studies. TNF-α 308GG genotype demonstrated trends toward increased sepsis risk in the primary analysis of culture-proven sepsis (OR 1.18, 95% confidence interval [CI] 0.97–1.44). IL-10 1082GG genotype was associated with lower sepsis odds in very low-birth-weight (VLBW) infants (OR 0.51, 95% CI 0.29–0.91).

Conclusion We uncovered an association between IL-10 1082 gene variation and sepsis in VLBW infants but did not identify associations between neonatal sepsis and TNF-α 308 or IL-6 gene variation. Larger cohort replication studies are required to validate these findings.

Keywords

genetic variation - systematic review - meta-analysis - infant - infection - genetic association studies

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References
1 Stoll BJ, Hansen NI, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3) 443-456
2 Stoll BJ, Hansen NI, Adams-Chapman I , et al; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292 (19) 2357-2365
3 Wynn JL, Cvijanovich NZ, Allen GL , et al. The influence of developmental age on the early transcriptomic response of children with septic shock. Mol Med 2011; 17 (11–12): 1146-1156
4 Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS. The host response to sepsis and developmental impact. Pediatrics 2010; 125 (5) 1031-1041
5 Boghossian NS, Page GP, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 2013; 162 (6) 1120-1124 , 1124.e1
6 Bizzarro MJ, Jiang Y, Hussain N, Gruen JR, Bhandari V, Zhang H. The impact of environmental and genetic factors on neonatal late-onset sepsis. J Pediatr 2011; 158 (2) 234-238.e1
7 Bhandari V, Bizzarro MJ, Shetty A , et al; Neonatal Genetics Study Group. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 2006; 117 (6) 1901-1906
8 Abu-Maziad A, Schaa K, Bell EF , et al. Role of polymorphic variants as genetic modulators of infection in neonatal sepsis. Pediatr Res 2010; 68 (4) 323-329
9 Chauhan M, McGuire W. Interleukin-6 (-174C) polymorphism and the risk of sepsis in very low birth weight infants: meta-analysis. Arch Dis Child Fetal Neonatal Ed 2008; 93 (6) F427-F429
10 Tiancha H, Huiqin W, Jiyong J, Jingfen J, Wei C. Association between lymphotoxin-α intron +252 polymorphism and sepsis: a meta-analysis. Scand J Infect Dis 2011; 43 (6–7): 436-447
11 Teuffel O, Ethier MC, Beyene J, Sung L. Association between tumor necrosis factor-alpha promoter -308 A/G polymorphism and susceptibility to sepsis and sepsis mortality: a systematic review and meta-analysis. Crit Care Med 2010; 38 (1) 276-282
12 Watanabe E, Buchman TG, Hirasawa H, Zehnbauer BA. Association between lymphotoxin-alpha (tumor necrosis factor-beta) intron polymorphism and predisposition to severe sepsis is modified by gender and age. Crit Care Med 2010; 38 (1) 181-193
13 Harding D, Dhamrait S, Millar A , et al. Is interleukin-6 -174 genotype associated with the development of septicemia in preterm infants?. Pediatrics 2003; 112 (4) 800-803
14 Ahrens P, Kattner E, Köhler B , et al; Genetic Factors in Neonatology Study Group. Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants. Pediatr Res 2004; 55 (4) 652-656
15 Baier RJ, Loggins J, Yanamandra K. IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants. BMC Med 2006; 4: 10 . Doi: 10.1186/1741-7015-4-10
16 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151 (4) 264-269 , W64
17 Little J, Higgins JP, Ioannidis JP , et al. STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE Statement. Ann Intern Med 2009; 150 (3) 206-215
18 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
19 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
20 Stoll BJ, Hansen N, Fanaroff AA , et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1): 285-291
21 Sørensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 1988; 318 (12) 727-732
22 Cooke GS, Hill AV. Genetics of susceptibility to human infectious disease. Nat Rev Genet 2001; 2 (12) 967-977
23 Härtel C, Hemmelmann C, Faust K , et al; German Neonatal Network. Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants. Crit Care Med 2011; 39 (5) 1190-1195
24 Ouyang L, Lv YD, Hou C, Wu GB, He ZH. Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis. Mol Biol Rep 2013; 40 (7) 4327-4332
25 Zhang AQ, Pan W, Gao JW , et al. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis. BMC Med Genet 2014; 15: 8
26 Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24 (1) 1-8
27 Hilgendorff A, Heidinger K, Pfeiffer A , et al. Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants. Genes Immun 2007; 8 (8) 671-677
28 Dzwonek AB, Neth OW, Thiébaut R , et al. The role of mannose-binding lectin in susceptibility to infection in preterm neonates. Pediatr Res 2008; 63 (6) 680-685
29 van der Zwet WC, Catsburg A, van Elburg RM, Savelkoul PH, Vandenbroucke-Grauls CM. Mannose-binding lectin (MBL) genotype in relation to risk of nosocomial infection in pre-term neonates in the neonatal intensive care unit. Clin Microbiol Infect 2008; 14 (2) 130-135
30 Aydemir C, Onay H, Oguz SS , et al. Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit. J Matern Fetal Neonatal Med 2011; 24 (9) 1124-1127
31 Auriti C, Prencipe G, Inglese R , et al. Role of mannose-binding lectin in nosocomial sepsis in critically ill neonates. Hum Immunol 2010; 71 (11) 1084-1088
32 Koroglu OA, Onay H, Erdemir G , et al. Mannose-binding lectin gene polymorphism and early neonatal outcome in preterm infants. Neonatology 2010; 98 (4) 305-312
33 Özkan H, Köksal N, Çetinkaya M , et al. Serum mannose-binding lectin (MBL) gene polymorphism and low MBL levels are associated with neonatal sepsis and pneumonia. J Perinatol 2012; 32 (3) 210-217
34 Härtel C, König I, Köster S , et al. Genetic polymorphisms of hemostasis genes and primary outcome of very low birth weight infants. Pediatrics 2006; 118 (2) 683-689
35 John Baier R, Loggins J, Yanamandra K. Angiotensin converting enzyme insertion/deletion polymorphism does not alter sepsis outcome in ventilated very low birth weight infants. J Perinatol 2005; 25 (3) 205-209
36 Derzbach L, Bokodi G, Treszl A, Vásárhelyi B, Nobilis A, Rigó Jr J. Selectin polymorphisms and perinatal morbidity in low-birthweight infants. Acta Paediatr 2006; 95 (10) 1213-1217
37 Spiegler J, Gilhaus A, Konig IR , et al. Polymorphisms in the renin-angiotensin system and outcome of very-low-birthweight infants. Neonatology 2010; 97 (1) 10-14
38 Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet 2001; 29 (3) 306-309
39 Stroup DF, Berlin JA, Morton SC , et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
40 Ioannidis JP, Trikalinos TA, Khoury MJ. Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. Am J Epidemiol 2006; 164 (7) 609-614
41 Man M, Close SL, Shaw AD , et al. Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis. Pharmacogenomics J 2013; 13 (3) 218-226

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