Open Access Highly Accessed Research article

Sequencing of the IL6 gene in a case–control study of cerebral palsy in children

Pouya Khankhanian1*, Sergio E Baranzini1, Britt A Johnson1, Lohith Madireddy1, Dorothee Nickles1, Lisa A Croen2 and Yvonne W Wu13*

Author Affiliations

1 Department of Neurology, University of California, 675 Nelson Rising Lane, 94158, San Francisco, CA, USA

2 Kaiser Permanente Division of Research, 2000 Broadway, 94612, Oakland, CA, USA

3 Department of Pediatrics, University of California, 350 Parnassus, Ste 609, 94117, San Francisco, CA, USA

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BMC Medical Genetics 2013, 14:126  doi:10.1186/1471-2350-14-126

Published: 7 December 2013

Abstract

Background

Cerebral palsy (CP) is a group of nonprogressive disorders of movement and posture caused by abnormal development of, or damage to, motor control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795, in the promoter region of the interleukin-6 (IL6) gene has been implicated in the pathogenesis of CP by mediating IL-6 protein levels in amniotic fluid and cord plasma and within brain lesions. This SNP has been associated with other neurological, vascular, and malignant processes as well, often as part of a haplotype block.

Methods

To refine the regional genetic association with CP, we sequenced (Sanger) the IL6 gene and part of the promoter region in 250 infants with CP and 305 controls.

Results

We identified a haplotype of 7 SNPs that includes rs1800795. In a recessive model of inheritance, the variant haplotype conferred greater risk (OR = 4.3, CI = [2.0-10.1], p = 0.00007) than did the lone variant at rs1800795 (OR = 2.5, CI = [1.4-4.6], p = 0.002). The risk haplotype contains one SNP (rs2069845, CI = [1.2-4.3], OR = 2.3, p = 0.009) that disrupts a methylation site.

Conclusions

The risk haplotype identified in this study overlaps with previously identified haplotypes that include additional promoter SNPs. A risk haplotype at the IL6 gene likely confers risk to CP, and perhaps other diseases, via a multi-factorial mechanism.

Keywords:
Cerebral palsy; Sanger sequencing; IL-6; Interleukin-6; Haplotype