Souza Matheus, Al-Sharif Lubna, Diaz Ivanna, Mantovani Alessandro, Villela-Nogueira Cristiane Alves
Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
An-Najah National University, Nablus, Palestine.
J Clin Exp Hepatol. 2025 May-Jun;15(3):102495. doi: 10.1016/j.jceh.2024.102495. Epub 2024 Dec 26.
BACKGROUND & AIMS: rs738409 variant is a risk factor for onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess its global prevalence, clinical and histological characteristics, and long-term outcomes in patients with MASLD.
PubMed and Embase databases were searched until December 30, 2023, for observational studies on genotyped adults with MASLD. Proportions were pooled using a generalized linear mixed model with Clopper-Pearson intervals. Continuous and dichotomous variables were analyzed using the DerSimonian-Laird method. International Prospective Register of Systematic Reviews registration number: CRD42023449838.
A total of 109 studies involving 118,302 individuals with MASLD were identified. The overall minor allele frequency of the G allele [MAF(G)] at was 0.45 (95% confidence interval [CI]: 0.43; 0.48) with high heterogeneity (I = 98%). The highest MAF(G) was found in Latin America (0.63) and the lowest in Europe (0.38). No African countries were identified. Carriers of the variant had reduced adiposity, altered fat metabolism, and worse liver damage/histology than noncarriers. There was significant heterogeneity in the clinical/histological analyses (I > 50%). Only the GG genotype was associated with higher mortality and liver-related events with no heterogeneity (I = 0%). Metaregressions showed the influence of adiposity, age, diabetes mellitus, and glucose on some expression parameters. Overall, there was a moderate risk of bias in the included studies.
This study reveals the global pattern of and its clinical, histological, and outcome implications in MASLD. Patients with MASLD and variant have different clinical features and worse liver severity, and only GG has a higher risk of mortality and liver outcomes. Our findings highlight the importance of genotyping in clinical trials and advocate for personalized medicine approaches.
rs738409变异是代谢功能障碍相关脂肪性肝病（MASLD）发病和进展的危险因素。我们旨在评估其在MASLD患者中的全球患病率、临床和组织学特征以及长期预后。
检索PubMed和Embase数据库至2023年12月30日，以查找关于成年MASLD基因分型患者的观察性研究。使用带有Clopper-Pearson区间的广义线性混合模型汇总比例。使用DerSimonian-Laird方法分析连续和二分变量。国际系统评价前瞻性注册编号：CRD42023449838。
共确定了109项研究，涉及118302例MASLD患者。rs738409位点G等位基因的总体次要等位基因频率[MAF(G)]为0.45（95%置信区间[CI]：0.43；0.48），异质性较高（I² = 98%）。MAF(G)在拉丁美洲最高（0.63），在欧洲最低（0.38）。未发现来自非洲国家的研究。该变异的携带者比非携带者肥胖程度降低、脂肪代谢改变且肝损伤/组织学更差。临床/组织学分析存在显著异质性（I²>50%）。只有rs738409 GG基因型与较高的死亡率和肝脏相关事件相关，且无异质性（I² = 0%）。Meta回归显示肥胖、年龄、糖尿病和血糖对某些rs738409表达参数有影响。总体而言，纳入研究存在中度偏倚风险。
本研究揭示了rs738409在MASLD中的全球模式及其临床、组织学和预后意义。携带rs738409变异的MASLD患者具有不同的临床特征和更严重的肝脏病变，只有rs738409 GG基因型具有更高的死亡风险和肝脏相关预后风险。我们的研究结果强调了rs738409基因分型在临床试验中的重要性，并提倡采用个性化医疗方法。
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