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Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1 m1 (T > C) and m2 (A > G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All subjects were genotyped for CYP1A1 m1 (T > C) and m2 (A > G) using PCR-RFLP with statistical analysis by using SPSS version 16.0 and VassarStats (online). Among the two gene variants rs4646903 (T > C) and rs1048943 (A > G), individuals with AG and GG genotypes of CYP1A1 m2 polymorphism have significantly higher and increased risk of cervical cancer (OR = 2.0, 95%CI = 1.04-3.84, p = 0.035; OR = 62.9, 95%CI = 3.72-1063.83, p = 0.004 respectively) and the association of CYP1A1 m1 polymorphism did not show any significant relationship with cervical cancer patients (p = 0.23). The ‘G’ allele showed strong association with the disease (p < 0.0001). Thus, CYP1A1 m2 polymorphism showed an increased risk in the population leading to cervical cancer. Our study suggested that the presence of ‘C’ allele of rs4646903 (T > C) showed no risk and ‘G’ allele of rs1048943 (A > G) might be a leading allele to cause increased cervical cancer susceptibility due to significant association of CYP1A1 m2 gene polymorphism. [ABSTRACT FROM AUTHOR]

Abstract: Interferon beta1 (IFNB1) is a type I interferon that is mainly known for its antiviral activity, but it also regulates a number of anti-inflammatory and immunomodulatory functions. Studies on mouse models of cerebral malaria have established that IFNB1 regulates severe malaria pathogenesis and increases overall survival against malaria. It down-regulates pro-inflammatory cytokines: TNF, IFNG and ICAM-1, resulting in decreased adherence of Plasmodium falciparum parasitized RBC to capillary wall, entry into the brain and delayed onset of death. Therefore, we hypothesized that variations in IFNB1 gene could regulate malarial pathogenesis. We re-sequenced the complete IFNB1 gene along with 900bp of 5′ up-stream and 500bp of 3′-UTR in 437 individuals from malaria endemic regions of the Orissa and Chhattisgarh states of India. The subjects comprised of 173 cases of severe malaria, 101 of mild malaria, and 156 ethnically matched asymptomatic controls. Data were statistically compared between cases and controls for their possible association with P. falciparum malarial outcome. Two single nucleotide polymorphisms (SNPs): a synonymous c.153C>T (rs1051922) and a non-synonymous substitution c.102C>G (rs139262191, p.Ser34Arg) were identified. The genotype and allele distribution of c.153C>T did not differ significantly between the study groups [mild, χ 2 2 =4.10, p-value<0.13 and severe χ 2 2 =0.06, p-value<0.97]. Interestingly, the rare non-synonymous SNP (rs139262191) was observed only in malaria patients. The differences between all cases and controls did not reach statistical significance, however, a statistically significant difference was observed between the asymptomatic control group and the cerebral malaria group [OR=20.32, 95% CI=1.08–382.63, p-value=0.044]. Moreover, the genotypes between cerebral malaria positive and negative groups were not significantly different [OR=5.58, 95% CI=0.61–50.97, p-value=0.123]. Our findings suggest that the IFNB1 variant, p.Ser34Arg, might be a risk factor for cerebral malaria in Indian populations. [Copyright &y& Elsevier]