Blomquist Sarah A, Albrecht Jil H, Hallmark Brian, Klimentidis Yann C, Garcia Luis A, Mandarino Lawrence J, Coletta Dawn K, Chilton Floyd H
School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States.
Department of Medicine, College of Medicine Tucson, and Asthma and Airway Diseases Research Center, University of Arizona Health Sciences, Tucson, AZ, United States.
Front Nutr. 2025 Mar 10;12:1538505. doi: 10.3389/fnut.2025.1538505. eCollection 2025.
Latinos, the largest racial/ethnic minority group in the United States, have high rates of cardiometabolic diseases, hypothesized due in part to genetic variation in the fatty acid desaturase () cluster that is associated with reduced omega-3 (n-3) highly unsaturated fatty acid (HUFA) biosynthesis. This study examined how variations in and other HUFA pathway-related genes ( and ) impact cardiometabolic disease risk factors in Latinos of Mexican Ancestry (LMA).
This study analyzed 493 self-identified LMA from the Arizona Insulin Resistance registry (AIR) and found a marked enrichment in alleles linked the ancestral haplotype (AH) compared to European Americans. LMA individuals with two AH alleles produced markedly lower levels of n-6 and n-3 HUFAs. However, this was more pronounced with the n-3 HUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), where the n-6 arachidonic acid (ARA) to EPA and DHA ratios were 30:1 and 5:1, respectively, and circulating EPA levels were reduced to <5 ng/mL. Importantly, genetic variations in both and regions also were strongly associated with several cardiometabolic disease (CMD) markers, with the presence of two AH alleles corresponding to a 45, 33, and 41% increase in fasting insulin, triglyceride levels and HOMA-IR, respectively.
This study reveals the potential impact of genetically influenced HUFA regulation and n-3 HUFA deficiency on cardiometabolic disease risk within LMA. These insights provide a strong rationale for future studies and clinical trials that focus on n-3 HUFA supplementation to mitigate CMD disparities in LMA populations.
拉丁裔是美国最大的种族/族裔少数群体，患有心血管代谢疾病的比例很高，部分原因推测是脂肪酸去饱和酶（）簇中的基因变异，该变异与ω-3（n-3）高度不饱和脂肪酸（HUFA）生物合成减少有关。本研究探讨了和其他与HUFA途径相关的基因（和）的变异如何影响墨西哥裔拉丁裔（LMA）的心血管代谢疾病风险因素。
本研究分析了来自亚利桑那胰岛素抵抗登记处（AIR）的493名自我认定的LMA，并发现与欧洲裔美国人相比，与祖先单倍型（AH）相关的等位基因明显富集。具有两个AH等位基因的LMA个体产生的n-6和n-3 HUFA水平明显较低。然而，n-3 HUFA、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的情况更为明显，其中n-6花生四烯酸（ARA）与EPA和DHA的比例分别为30:1和5:1，循环中的EPA水平降至<5 ng/mL。重要的是，和区域的基因变异也与几种心血管代谢疾病（CMD）标志物密切相关，存在两个AH等位基因分别对应空腹胰岛素、甘油三酯水平和HOMA-IR增加45%、33%和41%。
本研究揭示了基因影响的HUFA调节和n-3 HUFA缺乏对LMA中心血管代谢疾病风险的潜在影响。这些见解为未来专注于补充n-3 HUFA以减轻LMA人群中CMD差异的研究和临床试验提供了有力的理论依据。
