IL6 (∿74G/C) SNP but not IL4 (∿90C/T) polymorphisms contributes to the development of acute lymphoblastic leukemia, and is involved in gender specific risk in Mexican children

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• 作者：Betsy Gonzalez^a ; ^b ; Hilario Flores-A^a ; ^b ; Diego Sanchez^b ; Carmen Alaez^a ; Clara Gorodezky^a ; ^b
• 刊名：Human Immunology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：76
• 期：supp_S
• 页码：94
• 全文大小：35 K

文摘

The characteristic of acute lymphoblastic leukemia (ALL) is the clonal proliferation and accumulation of immature lymphoid cells. About 80% of children are cured with the nowadays treatment. IL-6 contributes to the systemic effects of inflammation in innate immunity but in adaptive immunity, it stimulates the growth of B-cells and acts as a growth factor for myeloma cells. IL-4 suppresses cellular immunity stimulating the development of TH2/Tc2 cells. ALL patients present high populations of IL-4 producer cells, with higher levels of IL-6. Variation in SNPs may lead to differential gene transcription, translation and protein structure. The purpose of this study was to evaluate the role of IL6 (−174G/C) and IL4 (−590C/T) SNPs in the development of ALL in Mexican children.

Methods

A total of 149 (58.4% were males) and 145 (58.6% were males) ALL patients and 376 controls were genotyped for IL4 and IL6 respectively. The patients were aged 1–17 and all of them are Mexican Mestizos born in Mexico. DNA was obtained from blood samples using a Maxwell16 instrument. Allele discrimination of IL6 −174G/C (rs1800795) and IL4-590C/T (rs2243250) was performed using a Taqman real time PCR assay on an ABI 7500 Real-Time PCR System. The study meets the criteria of the declaration of Helsinki.

Results

A low risk for ALL development may be associated with IL6 (−174 G/C) SNP, since the GC genotype was decreased in the patients(OR = 0.53; CI 0.31–0.91; p = 0.02). The frequency of IL6 (−174G/C) stratified by sex, showed a higher risk for the CC genotype in males (OR = 5.16; CI 1.02–26.21; p = 0.02). No association was found with ALL and IL4 (−590C/T) alleles/genotypes. The allele distribution of healthy controls is in Hardy–Weinberg equilibrium.

Conclusions

We suggest a protective role of IL6 (−174 GC) GC genotype that confers a lower risk for the development of ALL in Mexican Mestizo children and a higher risk for males carrying the CC genotype, agreeing with published data. IL-6 is a pro-inflammatory cytokine that regulates immune reactions in acute phases. The GC genotype that produces higher levels of IL-6 may confer a lower risk for the development of ALL, whilst CC genotype which is a low IL-6 producer may be of high risk in males, as pointed out by others. These data together with HLA results, may be helpful in transplantation