Genetic Factors Influence Risk of Mother-to-child Hepatitis C Virus Transmission

Differences in the HLA-DRB1 genetic locus were associated with variations in the risk of mother-to-child transmission of hepatitis C virus (HCV), according to a study published in the July 20, 2009 issue of Virology. A mismatch between genes carried by a mother and her infant appeared to confer protection against transmission.

Elena Bevilacqua and colleagues from Italy investigated the role of genetic factors in vertical HCV transmission.

The overall rate of HCV infection among infants born to HCV positive mothers is about 5%, the researchers noted as background. HIV coinfection and high maternal HCV viral load have been linked to increased transmission risk in prior studies. The only genetic factor previously evaluated is the HLA (human leukocyte antigen) complex, also known as the major histocompatibility complex, a large set of genes related to immune function.

The investigators focused on genes already known to be associated with HCV infection (HLA-DRB1, MBL2, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma, and interleukin 10 [IL-10]) or with liver disease progression (hemochromatosis [HFE] and TGF-beta1).

The analysis included 384 Italian patients:

	38 mother/child pairs in which both were HCV infected (indicating vertical transmission had occurred);
	104 HCV positive mothers with 114 HCV negative children (indicating no transmission);
	21 additional vertically infected HCV positive children;
	69 additional HCV-exposed but uninfected children.

Blood samples were analyzed to look for previously described polymorphisms, or variations at a single position, in these genes.

Results

	In mothers, the HLA-DRB104 variation correlated with a significantly lower rate of vertical HCV transmission (P = 0.023).
	In children, the HLA-DRB110 variation was associated with an increased risk of transmission (P = 0.036).
	Analysis of concordance, or matches, in HLA-DRB1 variations revealed that a HLA mismatch between mother and child was protective against HCV transmission (P = 0.017).

These findings, the investigators concluded, indicate that alloreactive immune responses -- or maternal immune responses to genetic material different from her own -- are involved in preventing vertical transmission of HCV.

Servizio di Genetica Medica, IRCCS Burlo Garofolo, Trieste, Italy; Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health & Great Ormond Hospital for Children, University College London, London, UK; Dipartimento di Scienze Pediatriche e dell'Adolescenza & Dipartimento di Genetica Biologia e Biochimica & Dipartimento di Pediatria, Università di Torino, Torino, Italy; Dipartimento di Pediatria, IRCCS Policlinico San Matteo, Pavia, Italy; Ospedale Infantile Regina Margherita, Torino, Italy; Clinica Malattie Infettive, Università di Genova, Genova, Italy; Università di Milano, Ospedale Sacco & Ospedale San Paolo, Milano, Italy; Ospedale Santa Chiara, Trento, Italy; Università di Bologna, Bologna, Italy; Università Federico II, Napoli, Italy; Clinica Pediatrica, Università del Piemonte Orientale, Novara, Italy.

9/01/09

Reference
E Bevilacqua, A Fabris, P Floreano, and others. Genetic factors in mother-to-child transmission of HCV infection. Virology 390(1): 64-70. July 20, 2009.