PMID- 33808990 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20221207 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 12 IP - 3 DP - 2021 Mar 12 TI - The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis. LID - 10.3390/genes12030404 [doi] LID - 404 AB - (1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor alpha (ERalpha) has been considered to play a key role due to a large gender difference in its expression. ERalpha is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I(2): 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I(2): 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies. FAU - Huang, Yu-Hao AU - Huang YH AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan. FAU - Fang, Wen-Hui AU - Fang WH AD - Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. FAU - Tsai, Dung-Jang AU - Tsai DJ AUID- ORCID: 0000-0002-5531-0810 AD - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan. AD - School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan. FAU - Chen, Yu-Hsuan AU - Chen YH AD - School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan. FAU - Wang, Yu-Chiao AU - Wang YC AD - School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan. AD - Department of Education & Medical Research, Taoyuan Armed Forces General Hospital, Taoyuan 325, Taiwan. FAU - Su, Wen AU - Su W AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 11490, Taiwan. FAU - Kao, Chung-Cheng AU - Kao CC AD - Superintendent's Office, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei 10581, Taiwan. FAU - Yi, Kevin AU - Yi K AD - Department of Biochemistry, Purdue University, West Lafayette, IN 47907-2063, USA. FAU - Wang, Chih-Chien AU - Wang CC AD - Department of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan. FAU - Su, Sui-Lung AU - Su SL AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan. AD - School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20210312 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) SB - IM MH - Aged MH - Alleles MH - Asian People/*genetics MH - Case-Control Studies MH - Estrogen Receptor alpha/*genetics MH - Female MH - Genetic Predisposition to Disease/*genetics MH - Humans MH - Male MH - Odds Ratio MH - Osteoarthritis, Knee/*genetics MH - Polymorphism, Genetic/genetics MH - Risk Factors PMC - PMC7999595 OTO - NOTNLM OT - ESR1 XbaI OT - estrogen receptor 1 (ESR1) OT - meta-analysis OT - osteoarthritis (OA) OT - polymorphism OT - rs9340799 OT - trial sequential analysis COIS- The authors have no conflict of interest to declare. EDAT- 2021/04/04 06:00 MHDA- 2021/08/04 06:00 PMCR- 2021/03/12 CRDT- 2021/04/03 01:31 PHST- 2021/01/15 00:00 [received] PHST- 2021/02/25 00:00 [revised] PHST- 2021/03/09 00:00 [accepted] PHST- 2021/04/03 01:31 [entrez] PHST- 2021/04/04 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2021/03/12 00:00 [pmc-release] AID - genes12030404 [pii] AID - genes-12-00404 [pii] AID - 10.3390/genes12030404 [doi] PST - epublish SO - Genes (Basel). 2021 Mar 12;12(3):404. doi: 10.3390/genes12030404.