Pravin Kesarwani et al Asian Pacific Journal of Cancer Prevention, Vol 9, 2008 76 Asian Pacific J Cancer Prev, 9, 76-80 Introduction Single nucleotide polymorphisms or SNPs and variable number of tandem repeats (VNTR) are common type of polymorphisms. The variants of DNA sequence can have a major impact on how humans respond to disease; environmental insults such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies. SNPs do not cause disease, but they can help determine the likelihood that a particular individual may develop a particular disease (http://www.ornl.gov/sci/techresources/ Human_Genome/faq/snps.shtml). In recent years there has been an enormous effort by numerous laboratories worldwide to identify the particular SNPs and VNTRs that play a major role in genetic predisposition to and disease progression in particular disease and cancers. Polymorphisms within the cytokine genes can play a role in the level of production of cytokines. Cytokines are small molecules secreted by cells in response to specific stimuli and alter the behavior of the same or other cells. Cytokines act on target cells generally within the hematopoietic system by binding to specific receptors, initiating signal transduction and second messenger pathways within the target cell. Cytokines function as highly complex and coordinated network in which they modulate their own synthesis as well as that *For Correspondence: Department of Urology, SGPGIMS, Raebareli Road, Lucknow-226014, India Phone No: 091-522-668004- 8, Ext. 2116 Fax : 091-522-2668 017 E-mail: ramamittal@yahoo.com rmittal@sgpgi.ac.in Abstract Variations in the production and activity of cytokines have been reported by several investigators which influence the susceptibility and/or resistance to various infectious agents and cancer. Differences in the cytokine production between individuals are often caused by single nucleotide polymorphism (SNP) in the promoter or coding regions of cytokine genes. Although the SNP cytokine gene variations are basically mutations, they are designated as polymorphisms, because these changes do not modify the alleles to rare or abnormal variants. The two important cytokine genes IL-4 and IL-6 of 343 unrelated healthy individuals from North India were compared with the published polymorphism of other populations. It was seen that our population differs from South Indian population as well as from other Caucasian populations except, Taiwanese population at IL-4 locus and Spanish and Polish population at the IL-6 gene locus. This study may be helpful for predicting clinical outcome of various infectious and immunoregulated disorders as well as explore for risk alleles for various cancers. Key Words: Cytokines - polymorphisms - international comparison of other cytokines and cytokine receptors. Production of numerous cytokines by immune cells in response to both antigen specific and -nonspecific stimuli is critical to the outcome of inflammatory immune responses. IL-4 and IL-6 are considered important cytokines as they play an important role in B-cell activation and differentiation (Kishimoto, 1989). These may be of major help in cancer prevention. IL-4 an anti-inflammatory cytokine plays a key role in activation and differentiation of B-cells, mast cells, erythroid progenitors and the development of the Th-2 subset of lymphocytes. Th2 cytokines such as IL-4, IL-2 and IL-10 primarily supports antibody production (Sosroseno et al., 1994). IL-4 is also known to inhibit macrophage activation and therefore may be involve in cancer. A variable number of tandem repeat (VNTR) of 70 base pair repeat is situated in third intronic region of the IL-4 gene. Three repeat allele is most common and two repeat allele is rare. There is another much rare allele of four repeat, which is reported only in few populations (Mout et al., 1991). Three repeat allele is known to be high producer of IL-4 (Nakashima et al., 2002). Interleukin-6 (IL-6) is a pleiotropic, proinflammatory cytokine involved in the regulation of the acute phase reaction, immune responses, and hematopoiesis. It has RESEARCH COMMUNICATION Do IL-4 Intron 3 VNTR and IL-6 (-174) G/C Variants Reflect Ethnic Variation? A Comparative Study Between the Global and North Indian Populations Pravin Kesarwani, Dinesh Ahirwar, Ranjana Singh, Parmeet K Manchanda, Rama D Mittal*