ABSTRACT
Background@#As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). @*Methods@#TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. @*Results@#In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively). @*Conclusion@#In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
ABSTRACT
Background@#As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). @*Methods@#TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. @*Results@#In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively). @*Conclusion@#In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
ABSTRACT
Although the association of genetic polymorphisms in glutathione S-transferase(GST) and N-acetyltransferase(NAT) with bladder cancer has been reported, limited numbers of studies have been indicated the association of CYP2E1 with bladder cancer, particularly in Asian population. A hospital based case-control study was conducted in South Korean, consisting of 232 histologically confirmed prevalent bladder cancer cases and 165 controls to evaluate the association between genetic polymorphisms of CYP2E1(RsaI) and development of bladder cancer. The frequency of CYP2E1(RsaI) c1/c1 genotype in bladder cancer cases was higher than in controls; 114 of 201(56.7%) vs. 62 of 146(42.5%). Men with CYP2E1(RsaI) c1/c1 genotype had increased risk of development of bladder cancer compared to men with at least one c2 allele(OR=1.7, 95% CI=1.1-2.7). The bladder cancer risk increased as the number of c1 allele increased(p for trend=0.005). The risk increased as the amount of smoking increased(p for trend=0.009). When data were analyzed for the interaction between smoking and CYP2E1 genetic polymorphisms, smokers with c1/c1 genotype have 2.5 greater risk in development of bladder cancer(95% CI=1.0-6.2) compared to nonsmokers with c2 allele(p for interaction=0.008). Our findings suggest that the interaction between genetic polymorphisms of CYP 2E1 (RsaI, c1/c1) and smoking may play an important role for development of bladder cancer among Koreans.