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Abstract Background Gout is a common disease resulting from hyperuricemia which causes acute arthritis. A recent genome-wide association study (GWAS) of gout identified three new loci for gout in Han Chinese: regulatory factor X3 (RFX3), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and breast carcinoma amplified sequence 3 (BCAS3). The lack of any replication studies of these three loci using other population groups prompted us to perform a replication study with Japanese clinically defined gout cases and controls. Methods We genotyped the variants of RFX3 (rs12236871), KCNQ1 (rs179785) and BCAS3 (rs11653176) in 723 Japanese clinically defined gout cases and 913 controls by TaqMan method. rs179785 of KCNQ1 is also evaluated by direct sequencing because of difficulties of its genotyping by TaqMan method. Results Although the variants of RFX3 and BCAS3 were clearly genotyped by TaqMan method, rs179785 of KCNQ1 was not, because rs179785 (A/G) of KCNQ1 is located at the last nucleotide (“A”) of the 12-bp deletion variant (rs200562977) of KCNQ1. Therefore, rs179785 and rs200562977 of KCNQ1 were genotyped by direct sequencing in all samples. Moreover, by direct sequencing with the same primers, we were able to evaluate the genotypes of rs179784 of KCNQ1 which shows strong linkage disequilibrium with rs179785 (D’ = 1.0 and r 2 = 0.99). rs11653176, a common variant of BCAS3, showed a significant association with gout (P = 1.66 × 10− 3; odds ratio [OR] = 0.80); the direction of effect was the same as that seen in the previous Han Chinese GWAS. Two variants of KCNQ1 (rs179785 and rs179784) had a nominally significant association (P = 0.043 and 0.044; OR = 0.85 and 0.86, respectively), but did not pass the significance threshold for multiple hypothesis testing using the Bonferroni correction. On the other hand, rs200562977 of KCNQ1 and rs12236871 of RFX3 did not show any significant association with gout. Conclusion BCAS3 is a coactivator of estrogen receptor alpha, and the influence of estrogen to serum uric acid level is well known. Our present replication study, as did the previous gout GWAS, demonstrated the common variant of BCAS3 to be associated with gout susceptibility.

Background: Gout is a common disease resulting from hyperuricemia which causes acute arthritis. A recent genome-wide association study (GWAS) of gout identified three new loci for gout in Han Chinese: regulatory factor X3 (RFX3), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and breast carcinoma amplified sequence 3 (BCAS3). The lack of any replication studies of these three loci using other population groups prompted us to perform a replication study with Japanese clinically defined gout cases and controls. Methods: We genotyped the variants of RFX3 (rs12236871), KCNQ1 (rs179785) and BCAS3 (rs11653176) in 723 Japanese clinically defined gout cases and 913 controls by TaqMan method. rs179785 of KCNQ1 is also evaluated by direct sequencing because of difficulties of its genotyping by TaqMan method. Results: Although the variants of RFX3 and BCAS3 were clearly genotyped by TaqMan method, rs179785 of KCNQ1 was not, because rs179785 (A/G) of KCNQ1 is located at the last nucleotide ("A") of the 12-bp deletion variant (rs200562977) of KCNQ1. Therefore, rs179785 and rs200562977 of KCNQ1 were genotyped by direct sequencing in all samples. Moreover, by direct sequencing with the same primers, we were able to evaluate the genotypes of rs179784 of KCNQ1 which shows strong linkage disequilibrium with rs179785 (D' = 1.0 and r2 = 0.99). rs11653176, a common variant of BCAS3, showed a significant association with gout (P = 1.66 × 10− 3; odds ratio [OR] = 0.80); the direction of effect was the same as that seen in the previous Han Chinese GWAS. Two variants of KCNQ1 (rs179785 and rs179784) had a nominally significant association (P = 0.043 and 0.044; OR = 0.85 and 0.86, respectively), but did not pass the significance threshold for multiple hypothesis testing using the Bonferroni correction. On the other hand, rs200562977 of KCNQ1 and rs12236871 of RFX3 did not show any significant association with gout. Conclusion: BCAS3 is a coactivator of estrogen receptor alpha, and the influence of estrogen to serum uric acid level is well known. Our present replication study, as did the previous gout GWAS, demonstrated the common variant of BCAS3 to be associated with gout susceptibility. [ABSTRACT FROM AUTHOR]

Studies have showed a number of susceptibility genes variants such as transcription factor 7-like 2 ( TCF7L2 ), potassium voltage-gated channel subfamily Q member 1 ( KCNQ1 ), juxtaposed with another zinc finger protein 1 ( JAZF1 ) and HNF1 homeobox B ( HNF1B ) been strongly associated with type 2 diabetes (T2D) in various ethnic groups. However, few studies have conducted in Uyghur, a Chinese minority ethnic group as an admixture population of Caucasians and East Asians. This study was performed to evaluate the association of genetic polymorphism with T2D susceptibility in the Uyghur population. The genomic samples from the blood of unrelated 284 T2D patients and 258 healthy controls were genotyped and analyzed using denaturing high performance liquid chromatography (DHPLC) assay. We found that four SNPs (rs290487, rs864745, rs4430796 and rs23136) in TCF7L2 , JAZF1 , HNF1B and KCNQ1 genetic regions show unique association with T2D in Uyghur population with an OR of 6.67295% (CI 1.06-1.48, P =0.002), an OR of 0.302 (CI 1.21-1.53, P =0.005) and an OR of 0.223 (CI 0.98-1.17, P =0.001), respectively. Subjects with mutant CC genotype of rs290487 were at high increased risk of T2D in Uyghur especially for the male subjects with an OR=11.782 (CI 1.12-1.53, P =0.001). Further metabolic evaluation confirmed that subject with rs290487 genotype have higher waste-hip circumference ratio ( P <0.05), diastolic blood pressure ( P <0.05), fasting blood glucose ( P <0.05) and hemoglobin A1c levels ( P <0.05). While mutant AA genotype for rs23136 (OR=0.223, CI 1.03-1.44, P =0.002) respectively were a protective factor in the Uyghur population. The rs231362 have also found been associated with fasting blood glucose and high-density lipoprotein respectively ( P <0.05). However, none of the genotypes showed the significant association with T2D in local Han Chinese population. Taken together, we confirmed the rs290487, rs231362 and rs4430796 transcription variants may act as genetic risk factors for the development of T2D in the Uyghur population in China and these results might provide supporting evidences for T2D diagnosis for Uyghur people in the future., Competing Interests: None., (IJCEP Copyright © 2017.)