We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 cases, 118,538 controls) from ethnically-diverse populations. We identified five new asthma loci, uncovered two additional novel associations at two known asthma loci, established asthma associations at two loci implicated previously in comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. Enrichment of asthma risk loci in enhancer marks, especially in immune cells, suggests a major role of these loci in the regulation of immune-related mechanisms.

The present study was designed to test whether common polymorphism G-50T within the promoter of human CYP2J2 gene is associated with increased risk of essential hypertension in a Russian population. We studied 576 unrelated subjects, including 295 patients with hypertension and 281 healthy subjects. Genotyping for polymorphism G-50T of the CYP2J2 gene was performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The frequency of a −50T variant allele of CYP2J2 gene was significantly higher in patients with hypertension versus healthy controls (OR 4.03 95%CI 1.80–9.04 p=0.0004). The association of a −50GT genotype with hypertension remained significant after adjustment for age, gender and family history of hypertension by multivariate logistic regression (OR 4.78 95%CI 1.87–12.27 p=0.001). It has been found that OR for −50GT genotype × gender interaction (OR 4.48 95%CI 1.93–10.39 p=0.00048) was slightly higher than OR for −50GT genotype (OR 4.43 95%CI 1.91–10.29 p=0.00052), suggesting a weak effect of gender on the risk of hypertension in the heterozygous carriers of −50GT genotype. A family history of hypertension has no effect on the association between a −50GT genotype and hypertension. In present study we demonstrate for the first time that a CYP2J2*7 allele of the CYP2J2 gene is clearly associated with an increased risk of essential hypertension. Furthermore, this study highlights the importance of P-450 epoxygenase pathway of arachidonic acid metabolism in the pathogenesis of hypertensive disease.

The aim of our pilot study was to evaluate the contribution of genes for xenobiotic-metabolizing enzymes (XMEs) for the development of bronchial asthma. We have genotyped 25 polymorphic variants of 18 key XME genes in 429 Russians, including 215 asthmatics and 214 healthy controls by a polymerase chain reaction, followed by restriction fragment length polymorphism analyses. We found for the first time significant associations of CYP1B1 V432L (P¼0.045), PON1 Q192R (P¼0.039) and UGT1A6 T181A (P¼0.025) gene polymorphisms with asthma susceptibility. Significant P-values were evaluated through Monte-Carlo simulations. The multifactor-dimensionality reduction method has obtained the best three-locus model for gene-gene interactions between three loci, EPHX1 Y113H, CYP1B1 V432L and CYP2D6 G1934A, in asthma at a maximum cross-validation consistency of 100% (P¼0.05) and a minimum prediction error of 37.8%. We revealed statistically significant gene-environment interactions (XME genotypes-smoking interactions) responsible for asthma susceptibility for seven XME genes. A specific pattern of gametic correlations between alleles of XME genes was found in asthmatics in comparison with healthy individuals. The study results point to the potential relevance of toxicogenomic mechanisms of bronchial asthma in the modern world, and may thereby provide a novel direction in the genetic research of the respiratory disease in the future.

Our pilot study was the first to show that gene-gene and gene-environment interactions in the AHR signaling pathway represent important determinants for the development of EH, and the pathway may become an attractive target for a pharmacological intervention in hypertensive patients in the future.

Gene encoding flavin-containing monooxygenase 3 (FMO3), a microsomal antioxidant defense enzyme, has been suggested to contribute to essential hypertension (EH). The present study was designed to investigate whether common functional polymorphism E158K (rs2266782) of the FMO3 gene is associated with EH susceptibility in a Russian population. A total of 2 995 unrelated subjects from Kursk (1 362 EH patients and 843 healthy controls) and Belgorod (357 EH patients and 422 population controls) regions of Central Russia were recruited for this study. DNA samples from all study participants were genotyped for the FMO3 gene polymorphism through PCR followed by RFLP analysis. We found that the polymorphism E158K is associated with increased risk of essential hypertension in both discovery population from Kursk region (OR 1.36 95% CI 1.09–1.69, P = 0.01) and replication population from Belgorod region (OR 1.54 95% CI 1.07–1.89, P = 0.02) after adjustment for gender and age using logistic regression analysis. Further analysis showed that the increased hypertension risk in carriers of genotype 158KK gene occurred in cigarette smokers, whereas nonsmoker carriers of this genotype did not show the disease risk. This is the first study reporting the association of the FMO3 gene polymorphism and the risk of essential hypertension.