Primer hipolipoproteinemili hastalarda monosit/yüksek yoğunluklu lipoprotein kolesterol oranı

Abstract

Amaç: Hipolipoproteinemi erişkinlerde kan lipid düzeylerindeki düşüklüktür. Genetik mutasyonlara bağlı primer hipolipoproteinemi nadir görülen bir durumdur. Hipolipoproteineminin klinik önemini gösteren çalışmalar sınırlıdır. Bu çalışmada primer hipolipoproteinemili hastaların klinik ve laboratuvar özelliklerinin ve monosit/yüksek yoğunluklu lipoprotein (HDL) oranının değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Primer hipolipoproteinemili sekiz hasta ile on iki sağlıklı kontrol grubunun lipid profilleri, monosit/HDL oranları, hemogram, akut faz yanıt testleri ve karaciğer testleri karşılaştırıldı. Bulgular: Trigliserid (TG), düşük yoğunluklu lipoprotein (LDL) ve total kolesterol (TK) düzeyleri hasta grubunda kontrol grubuna göre anlamlı derecede düşük bulundu (sırasıyla p=0,037 ve LDL ve TK’nın her ikisi için <0,001). HDL düzeyleri açısından gruplar arasında fark yoktu. Lipoprotein (a) (Lp(a)) düzeyleri hasta grubunda kontrol grubuna göre anlamlı derecede düşük bulundu (p=0,006). Absolü monosit sayısı (AMS) hasta grubunda kontrol grubuna göre anlamlı olarak yüksek bulundu (p=0,002). Monosit/HDL oranları (MHO) hasta grubunda kontrol grubuna göre anlamlı derecede yüksekti (p=0,016). MHO ile LDL arasında negatif korelasyon saptandı (p=0,001). Sonuç: Bu çalışmada primer hipolipoproteinemili hastalarda AMS ve MHO sağlıklı kontrol grubuna göre daha yüksek bulundu. Monositler, aterosklerotik hastalığın ilerlemesinin tüm aşamalarında yer alır. HDL’nin antiinflamatuar ve antioksidan etkileri ile aterosklerotik hastalıklarda koruyucu rolü olduğu bilinmektedir. Her ikisini birleştiren bir indeks olan MHR’nin kardiyovasküler hastalıklarda prognostik bir belirteç olduğu gösterilmiştir. Bilindiği kadarıyla bu çalışma, primer hipolipoproteinemi hastalarında MHO’yu araştıran ilk çalışmadır. Küçük örneklem büyüklüğüne ve dahil edilen hastaların heterojen doğasına rağmen yüksek AMS ve MHO düzeyleri mevcut çalışmanın en önemli bulgularıdır. Hipolipoproteinemili hastalara aterosklerotik hastalıklar için düşük risk atfedilmesine rağmen, yüksek AMS ve MHO, aterosklerotik hastalık riski açısından lipid redistribüsyonundaki değişiklikler nedeniyle bu hastaların dikkatle izlenmesi gerektiğine dair bir uyarı niteliğindedir.

Keywords

• Hipolipoproteinemiler
• hipobetalipoproteinemiler
• lipoprotein(a)
• monositler
• non alkolik yağlı karaciğer hastalığı

The monocyte/high-density lipoprotein cholesterol ratio in patients with primary hypolipoproteinemia

Abstract

Aim: Hypolipoproteinemia is low blood lipid levels in adults. Primary hypolipoproteinemia due to genetic mutations is a rare condition. Studies to demonstrate the clinical significance of hypolipoproteinemia are limited. It was aimed to evaluate the clinical and laboratory characteristics of patients with primary hypolipoproteinemia and the monocyte/high-density lipoprotein (HDL) ratio in this study. Material and Method: Eight patients with primary hypolipoproteinemia and twelve healthy control subjects were compared in terms of lipid profiles, monocyte/HDL ratios, hemogram, acute phase response tests, and liver tests. Results: Triglycerides (TG), low-density lipoprotein (LDL), and total cholesterol (TC) levels were found to be significantly lower in the patient group than in the control group (p=0.037 and <0.001 for LDL and TC both, respectively). There was no difference between the groups in terms of HDL levels. Lipoprotein (a) (Lp(a)) levels were found to be significantly lower in the patient group compared to the control group (p=0.006). Absolute monocyte count (AMC) was found to be significantly higher in the patient group than in the control group (p=0.002). Monocyte/HDL ratios (MHR) were significantly higher in the patient group than in the control group (p=0.016). There was a negative correlation between MHR and LDL (p=0.001). Conclusion: AMC and MHR were found higher in patients with primary hypolipoproteinemia than in the healthy control group in this study. Monocytes are involved in all stages of the progression of atherosclerotic disease. HDL is known to have a protective role in atherosclerotic diseases with its anti-inflammatory and antioxidant effects. MHR, which is an index that combines both, has been shown to be a prognostic marker in cardiovascular diseases. This study is the first to investigate MHR in primary hypolipoproteinemia patients. Despite the small sample size and the heterogeneous nature of the patients included high AMC and MHR levels are important findings of the current study. Although patients with hypolipoproteinemia are attributed to a low risk for atherosclerotic diseases, high AMC and MHR are a warning that these patients should be followed carefully due to changes in lipid redistribution in terms of the risk of atherosclerotic disease.

Keywords

• Hypolipoproteinemias
• hypobetalipoproteinemias
• lipoprotein(a)
• monocytes
• non-alcoholic fatty liver disease

References

1. Rosenson RS, Durrington P. Low LDL-cholesterol: etiologies and approach to evaluation. In: Post TW, editor. UpToDate. Waltham (MA): UpToDate. (accessed 2022 August 14).
2. Lee J, Hegele RA. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J Inherit Metab Dis 2014; 37: 333-9.
3. Peretti N, Sassolas A, Roy CC, et al. Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers. Orphanet J Rare Dis 2010; 5: 24.
4. Schonfeld G, Lin X, Yue P. Familial hypobetalipoproteinemia: genetics and metabolism. Cell Mol Life Sci 2005; 62: 1372-8.
5. Tarugi P, Averna M. Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum. Adv Clin Chem 2011; 54: 81-107.
6. Rosenson RS, Durrington P. HDL cholesterol: clinical aspects of abnormal values. In: Post TW, editor. UpToDate. Waltham (MA): UpToDate. (accessed 2022 August 14).
7. Minicocci I, Montali A, Robciuc MR, et al. Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization. J Clin Endocrinol Metab 2012; 97: E1266-75.
8. Sankatsing RR, Fouchier SW, de Haan S, et al. Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 2005; 25: 1979-84.

9. Utermann G. The mysteries of lipoprotein(a). Science 1989; 246: 904-10.
10. Visser ME, Witztum JL, Stroes ES, Kastelein JJ. Antisense oligonucleotides for the treatment of dyslipidaemia. Eur Heart J 2012; 33: 1451-8.
11. Averna M, Marcovina SM, Noto D, Cole TG, Krul ES, Schonfeld G. Familial hypobetalipoproteinemia is not associated with low levels of lipoprotein(a). Arterioscler Thromb Vasc Biol 1995; 15: 2165-75.
12. Soutar AK, McCarthy SN, Seed M, Knight BL. Relationship between apolipoprotein(a) phenotype, lipoprotein(a) concentration in plasma, and low density lipoprotein receptor function in a large kindred with familial hypercholesterolemia due to the pro664----leu mutation in the LDL receptor gene. J Clin Invest 1991; 88: 483-92.
13. Minicocci I, Santini S, Cantisani V, et al. Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. J Lipid Res 2013; 54: 3481-90.
14. Woollard KJ, Geissmann F. Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 2010; 7: 77-86.
15. Ganjali S, Gotto AM Jr, Ruscica M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol 2018; 233: 9237-46.
16. Chen JW, Li C, Liu ZH, et al. The role of monocyte to high-density lipoprotein cholesterol ratio in prediction of carotid intima-media thickness in patients with type 2 diabetes. Front Endocrinol (Lausanne) 2019; 10: 191.
17. Battaglia S, Scialpi N, Berardi E, et al. Gender, BMI and fasting hyperglycaemia influence monocyte to-HDL ratio (MHR) index in metabolic subjects. PLoS One 2020; 15: e0231927.
18. Yozgat A, Ekmen N, Kasapoglu B, Unsal Y, Sokmen FC, Kekilli M. Monocyte/HDL ratio in non-alcoholic hepatic steatosis. Arq Gastroenterol 2021; 58: 439-42.
19. Linton MF, Farese RV Jr, Young SG. Familial hypobetalipoproteinemia. J Lipid Res 1993; 34: 521-41.
20. Hartz J, Hegele RA, Wilson DP. Low LDL cholesterol-Friend or foe? J Clin Lipidol 2019; 13: 367-73.