Association analysis of polymorphisms of the CRHR1 gene with infantile spasms

Yang,Guang; Zou,Li-Ping; Wang,Jing; Shi,Xiu-Yu; Yang,Xiao-Fan; Wang,Bin; Liu,Yu-Jie; Sun,Yan-Hong; Jia,Fei-Yong

doi:10.3892/mmr.2015.3751

Association analysis of polymorphisms of the CRHR1 gene with infantile spasms

Authors:
- Guang Yang
- Li-Ping Zou
- Jing Wang
- Xiu-Yu Shi
- Xiao-Fan Yang
- Bin Wang
- Yu-Jie Liu
- Yan-Hong Sun
- Fei-Yong Jia
View Affiliations

Affiliations: Department of Pediatrics, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Pediatrics, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3751
Pages: 2539-2546
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

While >200 types of etiologies have been shown to be involved in the pathogenesis of infantile spasms, the pathophysiology of infantile spasms remains largely elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction were shown to be involved in the development of infantile spasms. To test the genetic association between the CRHR1 gene, which encodes the corticotrophin-releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128 cases with infantile spasms and 131 healthy controls. Correlation analysis was performed on the genotyped data. Under the assumption of the dominant model, the selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948, showed no association with the risk of infantile spasms and the effectiveness of adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis suggested none of them was associated with infantile spasms. In conclusion, the experimental results of the present study suggested no association between the CRHR1 gene and infantile spasms in a Chinese population.

View Figures

View References

1	Hrachovy RA and Frost JD Jr: Infantile spasms. Handb Clin Neurol. 111:611–618. 2013.PubMed/NCBI
2	Pavone P, Striano P, Falsaperla R, Pavone L and Ruggieri M: Infantile spasms syndrome, West syndrome and related phenotypes: What we know in 2013. Brain Dev. 36:739–751. 2014. View Article : Google Scholar
3	Trevathan E, Murphy CC and Yeargin-Allsopp M: The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 40:748–751. 1999. View Article : Google Scholar : PubMed/NCBI
4	Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S and Snead OC III; Child Neurology Society: Evidence-based guideline update: Medical treatment of infantile spasms Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 78:1974–1980. 2012. View Article : Google Scholar : PubMed/NCBI
5	Osborne JP, Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM and O’Callaghan FJ: The underlying etiology of infantile spasms (West syndrome): Information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. 51:2168–2174. 2010. View Article : Google Scholar : PubMed/NCBI
6	Sogawa Y and Moshe SL: Catastrophic epilepsies: Clinical controversies of infantile spasms. Neurol Asia. 15:5–7. 2010.
7	Paciorkowski AR, Thio LL and Dobyns WB: Genetic and biologic classification of infantile spasms. Pediatr Neurol. 45:355–367. 2011. View Article : Google Scholar : PubMed/NCBI
8	Shang NX, Zou LP, Zhao JB, Zhang F and Li H: Association between prenatal stress and infantile spasms: A case-control study in China. Pediatr Neurol. 42:181–186. 2010. View Article : Google Scholar : PubMed/NCBI
9	Wang YJ, Zhang Y, Liang XH, Yang G and Zou LP: Effects of adrenal dysfunction and high-dose adrenocorticotropic hormone on NMDA-induced spasm seizures in young Wistar rats. Epilepsy Res. 100:125–131. 2012. View Article : Google Scholar : PubMed/NCBI
10	Stafstrom CE: Infantile spasms: A critical review of emerging animal models. Epilepsy Curr. 9:75–81. 2009. View Article : Google Scholar : PubMed/NCBI
11	Baram TZ and Schultz L: Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat. Brain Res Dev Brain Res. 61:97–101. 1991. View Article : Google Scholar : PubMed/NCBI
12	Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, et al: Infantile spasms: A U.S. consensus report. Epilepsia. 51:2175–2189. 2010. View Article : Google Scholar : PubMed/NCBI
13	Brunson KL, Avishai-Eliner S and Baram TZ: ACTH treatment of infantile spasms: Mechanisms of its effects in modulation of neuronal excitability. Int Rev Neurobiol. 49:185–197. 2002.PubMed/NCBI
14	Wypior G, Jeschke U, Kurpisz M and Szekeres-Bartho J: Expression of CRH, CRH-related peptide and CRH receptor in the ovary and potential CRH signalling pathways. J Reprod Immunol. 90:67–73. 2011. View Article : Google Scholar : PubMed/NCBI
15	Zoumakis E, Kalantaridou SN and Makrigiannakis A: CRH-like peptides in human reproduction. Curr Med Chem. 16:4230–4235. 2009. View Article : Google Scholar : PubMed/NCBI
16	Hauger RL, Risbrough V, Brauns O and Dautzenberg FM: Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: New molecular targets. CNS Neurol Disord Drug Targets. 5:453–479. 2006. View Article : Google Scholar : PubMed/NCBI
17	Bogdan R, Santesso DL, Fagerness J, Perlis RH and Pizzagalli DA: Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning. J Neurosci. 31:13246–13254. 2011. View Article : Google Scholar : PubMed/NCBI
18	Liu Z, Liu W, Yao L, Yang C, Xiao L, Wan Q, Gao K, Wang H, Zhu F, Wang G, et al: Negative life events and corticotropin-releasing-hormone receptor1 gene in recurrent major depressive disorder. Sci Rep. 3:15482013. View Article : Google Scholar : PubMed/NCBI
19	Heim C, Bradley B, Mletzko TC, Deveau TC, Musselman DL, Nemeroff CB, Ressler KJ and Binder EB: Effect of childhood trauma on adult depression and neuroendocrine function: Sex-specific moderation by CRH receptor 1 gene. Front Behav Neurosci. 3:412009. View Article : Google Scholar
20	Chen AC, Manz N, Tang Y, Rangaswamy M, Almasy L, Kuperman S, Nurnberger J Jr, O’Connor SJ, Edenberg HJ, Schuckit MA, et al: Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. Alcohol Clin Exp Res. 34:988–996. 2010. View Article : Google Scholar : PubMed/NCBI
21	Engel J Jr; International League Against Epilepsy (ILAE): A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia. 42:796–803. 2001. View Article : Google Scholar : PubMed/NCBI
22	Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, et al: The structure of haplotype blocks in the human genome. Science. 296:2225–2229. 2002. View Article : Google Scholar : PubMed/NCBI
23	Lux AL: Latest American and European updates on infantile spasms. Curr Neurol Neurosci Rep. 13:3342013. View Article : Google Scholar : PubMed/NCBI
24	Brunson KL, Eghbal-Ahmadi M and Baram TZ: How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis. Brain Dev. 23:533–538. 2001. View Article : Google Scholar : PubMed/NCBI
25	Shi XY, Zou LP, Yang G and Ding YX: Prenatal stress exposure hypothesis for infantile spasms. Med Hypotheses. 78:735–737. 2012. View Article : Google Scholar : PubMed/NCBI
26	Liu ZL, He B, Fang F, Tang CY and Zou LP: Genetic polymorphisms of MC2R gene associated with responsiveness to adrenocorticotropic hormone therapy in infantile spasms. Chin Med J (Engl). 121:1627–1632. 2008.
27	Ding YX, Zou LP, He B, Yue WH, Liu ZL and Zhang D: ACTH receptor (MC2R) promoter variants associated with infantile spasms modulate MC2R expression and responsiveness to ACTH. Pharmacogenet Genomics. 20:71–76. 2010. View Article : Google Scholar : PubMed/NCBI
28	Ding YX, Zhang Y, He B, Yue WH, Zhang D and Zou LP: A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms. Dev Med Child Neurol. 52:1028–1032. 2010. View Article : Google Scholar : PubMed/NCBI
29	Wasserman D, Wasserman J and Sokolowski M: Genetics of HPA-axis, depression and suicidality. Eur Psychiatry. 25:278–280. 2010. View Article : Google Scholar : PubMed/NCBI
30	Aguilera G, Nikodemova M, Wynn PC and Catt KJ: Corticotropin releasing hormone receptors: Two decades later. Peptides. 25:319–329. 2004. View Article : Google Scholar : PubMed/NCBI
31	Geng LY, Ye DQ, Shi YY, Xu Z, Pu MJ, Li ZY, Li XL, Li Y and Zhang ZJ: Influence of genetic polymorphisms involved in the hypothalamic-pituitary-adrenal axis and their interactions with environmental factors on antidepressant response. CNS Neurosci Ther. 20:237–243. 2014. View Article : Google Scholar : PubMed/NCBI
32	Ray LA, Sehl M, Bujarski S, Hutchison K, Blaine S and Enoch MA: The CRHR1 gene, trauma exposure, and alcoholism risk: A test of G × E effects. Genes Brain Behav. 12:361–369. 2013. View Article : Google Scholar : PubMed/NCBI
33	Grabe HJ, Schwahn C, Appel K, Mahler J, Schulz A, Spitzer C, Fenske K, Barnow S, Lucht M, Freyberger HJ, et al: Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population. Am J Med Genet B Neuropsychiatr Genet. 153B:1483–1493. 2010. View Article : Google Scholar : PubMed/NCBI
34	Yang G, Zou LP, He B, Ding YX, Wang J, Shi XY, Sun YH and Jia FY: NR3C1 gene polymorphism for genetic susceptibility to infantile spasms in a Chinese population. Life Sci. 91:37–43. 2012. View Article : Google Scholar : PubMed/NCBI