Department of Anthropology, University of Delhi, India.
Genomic Research on Complex Diseases (GRC) Group, CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, Telangana-500007, India.
Ethn Dis. 2018 Oct 18;28(4):525-530. doi: 10.18865/ed.28.4.525. eCollection 2018 Fall.
Impaired homocysteine metabolism (IHM; hyperhomocysteinemia) has been linked with many complex disorders like cardiovascular diseases and immunological disturbances. However, studies understanding IHM in light of pro- and anti- atherogeneic markers like Interleukin-17A & -10 (IL-17A & IL-10) and Forkhead box p3 (Foxp3, a master transcription factor) are scarce.
In our present study, we aimed to understand the relation of IHM with plasma IL-17A and IL-10 levels and Foxp3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from an endogamous population (Jats of Haryana, North India) with high prevalence of IHM without the concurrence of significant adverse cardiovascular outcomes.
Forty (40) clinically healthy individuals, unrelated up to first cousins, were recruited and were subjected to demographic, physiological and anthropometric profiling, followed by intravenous blood sample collection (fasting) and lipid profiling. Plasma homocysteine levels were estimated and individuals with homocysteine levels ≥ 15umol/L and <15umol/L were categorized as the impaired homocysteine metabolism group (IHM, n=30) and normal homocysteine metabolism group (NHM, n=10) respectively. Plasma folate and vitamin B12 and MTHFR C677T (methylenetetrahydrofolate reductase) polymorphism were detected. Relative mRNA expression of Foxp3 in PBMCs (normalized to 18S) was quantitated using SyBR green technology. Plasma IL-10 & 17 levels were estimated by ELISA assays.
None of the physiological, anthropometric and lipid variables were different between the two groups. Foxp3 mRNA expression levels were relatively lower, and plasma IL-10 levels were found to be comparable among IHM and NHM group. However, significantly higher IL-17A levels and relatively high LDL cholesterol levels were present in the IHM group as compared with NHM. Our findings suggest that the Jats of Haryana, North India, exhibiting high levels of homocysteine, might also carry the high IL-17A -pro-atherogenic marker, suggesting an increasing burden of pre-morbid condition. This apparently does not reach to significant mortality/morbidity attributed to the counter action or balancing act of IL-10 (an anti-atherogenic marker). This further suggests environment-influenced epigenetic control mechanisms of the targeted genes in the present population.
同型半胱氨酸代谢受损（IHM；高同型半胱氨酸血症）与心血管疾病和免疫紊乱等许多复杂疾病有关。然而，关于前、后动脉粥样硬化标志物，如白细胞介素-17A 和 -10（IL-17A 和 IL-10）和叉头框 P3（Foxp3，主转录因子）与 IHM 的关系的研究很少。
在本研究中，我们旨在了解同型半胱氨酸代谢受损个体的外周血单个核细胞（PBMCs）中白细胞介素-17A 和白细胞介素-10 水平和 Foxp3 mRNA 表达与高同型半胱氨酸血症之间的关系，这些个体来自于一个具有高同型半胱氨酸血症患病率的同宗人群（印度哈里亚纳邦的 Jat 人），且没有发生显著不良心血管结局。
招募了 40 名（40 名）无血缘关系的直系亲属的临床健康个体，并对其进行了人口统计学、生理学和人体测量学分析，然后进行静脉采血（空腹）和血脂分析。估计血浆同型半胱氨酸水平，将同型半胱氨酸水平≥15μmol/L 和<15μmol/L 的个体分别归类为受损同型半胱氨酸代谢组（IHM，n=30）和正常同型半胱氨酸代谢组（NHM，n=10）。检测血浆叶酸和维生素 B12 及 MTHFR C677T（亚甲基四氢叶酸还原酶）多态性。使用 SyBR 绿色技术定量 PBMCs 中 Foxp3 的相对 mRNA 表达（标准化为 18S）。通过 ELISA 测定法测定血浆 IL-10 和 17 水平。
两组之间的生理、人体测量和血脂变量均无差异。IHM 和 NHM 组之间 Foxp3 mRNA 表达水平相对较低，且血浆 IL-10 水平相当。然而，与 NHM 组相比，IHM 组的 IL-17A 水平显著升高，且 LDL 胆固醇水平相对较高。我们的研究结果表明，印度哈里亚纳邦的 Jat 人，同型半胱氨酸水平较高，可能也携带高 IL-17A-促动脉粥样硬化标志物，表明存在增加的前期病态负担。这显然不会导致归因于 IL-10（一种抗动脉粥样硬化标志物）的作用或平衡作用的显著死亡率/发病率。这进一步表明，在本研究人群中，存在受环境影响的靶向基因的表观遗传控制机制。
