Association of Inflammatory Genes in Obstructive Sleep Apnea and Non Alcoholic Fatty Liver Disease in Asian Indians Residing in North India

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Jul 13

PMID 30001365

Citations 13

Authors

Surya Prakash Bhatt

Randeep Guleria

Naval K Vikram

S Vivekanandhan

Yogendra Singh

A K Gupta

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies have indicated that variants of the high sensitive C-reactive protein (CRP), Interleukin (IL)-6 and leptin receptor (LEPR) genes are associated with the presence of obstructive sleep apnea (OSA) but not in non-alcoholic fatty liver disease (NAFLD) in Asian Indians. The study was conducted to investigate the association of CRP rs1130864 (1444C/T), IL-6 rs1800795 (-174G/C) and LEPR rs1137101 (Q223R) genes with OSA and NAFLD in Asian Indians residing in North India.

Methods: 240 overweight/ obese subjects [body mass index (BMI>23kg/m2)], 124 with OSA and with NAFLD (group 1), 47 with OSA without NAFLD (group 2), 44 without OSA and with NAFLD (group 3) and 25 without OSA and without NAFLD (group 4) were recruited in this study. The severity of NAFLD was based on abdomen liver ultrasound and of OSA on overnight polysomnography. Clinical details, anthropometry profile, body composition, biochemical parameters and inflammatory markers were measured. Polymerase chain reaction and restriction fragment length polymorphism of CRP, IL-6 and LEPR gene was performed. The associations of these polymorphisms with clinical, anthropometric and biochemical profiles were investigated. The genotypes were confirmed by DNA sequencing analysis.

Results: The C, T and R alleles of IL-6, CRP and LEPR genes was more frequent in OSA and NAFLD subjects and significantly correlated with higher protein levels. The prevalence of variant genotypes C/T of CRP, G/C of IL-6 and Q/R of LEPR genes was significantly higher in OSA subjects as compared to non OSA subjects. Further, C/C genotype of IL-6 (G/C), T/T of CRP (C/T) and RR genotype of LEPR (Q/R) was associated with significantly higher BMI, fat mass (kg), % body fat, waist circumference, serum triglycerides, total cholesterol, alkaline phosphate, aspartate transaminase and fasting insulin levels in OSA and NAFLD subjects. Using a multivariate analysis, the combined effect of three polymorphisms of CRP, IL-6 and LEPR gene variants on OSA and NAFLD risk was evaluated. Odds ratio for OSA and NAFLD with the combination of the three gene polymorphisms increased to 2.84 (95% CI: 1.08-6.54; p = 0.04) even when adjusted for sex, age and BMI.

Conclusion: Polymorphisms of pro-inflammatory cytokine genes were associated with increased risk of OSA and NAFLD in Asian Indians.

Citing Articles

The Association Between the C-Reactive Protein Gene Variants rs1130864 and rs2794521 and Obstructive Sleep Apnea in the Iranian Kurdish Population.

Rasouli S, Alizadeh Severi A, Abdolsamadi M, Mohassel Y, Safari F, Salari F Genet Test Mol Biomarkers. 2024; 28(12):485-491.

PMID: 39628367 PMC: 11659465. DOI: 10.1089/gtmb.2024.0395.

Association of Obstructive Sleep Apnea with Nonalcoholic Fatty Liver Disease: Evidence, Mechanism, and Treatment.

Wang L, Liu H, Zhou L, Zheng P, Li H, Zhang H Nat Sci Sleep. 2024; 16:917-933.

PMID: 39006248 PMC: 11244635. DOI: 10.2147/NSS.S468420.

Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches.

Mahmoudi S, Tarzemani S, Aghajanzadeh T, Kasravi M, Hatami B, Zali M Eur J Med Res. 2024; 29(1):190.

PMID: 38504356 PMC: 10953212. DOI: 10.1186/s40001-024-01708-8.

Association of TNF-α (-308G/A) Gene Polymorphism with Changes in Circulating TNF-α Levels in Response to CPAP Treatment in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

Celik Y, Peker Y, Yucel-Lindberg T, Thelander T, Behboudi A J Clin Med. 2023; 12(16).

PMID: 37629366 PMC: 10455347. DOI: 10.3390/jcm12165325.

Management of non-alcoholic fatty liver disease patients with sleep apnea syndrome.

Sheng W, Ji G, Zhang L World J Gastroenterol. 2022; 28(43):6099-6108.

PMID: 36483151 PMC: 9724487. DOI: 10.3748/wjg.v28.i43.6099.

References

Prabhakar N, Kumar G . Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia. Respir Physiol Neurobiol. 2010; 174(1-2):156-61. PMC: 3042768. DOI: 10.1016/j.resp.2010.08.021. View

Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, Smith P . Chronic intermittent hypoxia predisposes to liver injury. Hepatology. 2007; 45(4):1007-13. DOI: 10.1002/hep.21593. View

Hanaoka M, Yu X, Urushihata K, Ota M, Fujimoto K, Kubo K . Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome. Chest. 2007; 133(1):79-85. DOI: 10.1378/chest.07-1633. View

Larkin E, Patel S, Goodloe R, Li Y, Zhu X, Gray-McGuire C . A candidate gene study of obstructive sleep apnea in European Americans and African Americans. Am J Respir Crit Care Med. 2010; 182(7):947-53. PMC: 2970865. DOI: 10.1164/rccm.201002-0192OC. View

Popko K, Gorska E, Wasik M, Stoklosa A, Plywaczewski R, Winiarska M . Frequency of distribution of leptin receptor gene polymorphism in obstructive sleep apnea patients. J Physiol Pharmacol. 2008; 58 Suppl 5(Pt 2):551-61. View

Misra A, Khurana L . Obesity and the metabolic syndrome in developing countries. J Clin Endocrinol Metab. 2008; 93(11 Suppl 1):S9-30. DOI: 10.1210/jc.2008-1595. View

Tumu V, Govatati S, Guruvaiah P, Deenadayal M, Shivaji S, Bhanoori M . An interleukin-6 gene promoter polymorphism is associated with polycystic ovary syndrome in South Indian women. J Assist Reprod Genet. 2013; 30(12):1541-6. PMC: 3843174. DOI: 10.1007/s10815-013-0111-1. View

Bhushan B, Guleria R, Misra A, Pandey R, Luthra K, Vikram N . Obstructive sleep apnoea correlates with C-reactive protein in obese Asian Indians. Nutr Metab Cardiovasc Dis. 2008; 19(3):184-9. DOI: 10.1016/j.numecd.2008.06.008. View

Gotoda T, Manning B, Goldstone A, Imrie H, Evans A, Strosberg A . Leptin receptor gene variation and obesity: lack of association in a white British male population. Hum Mol Genet. 1997; 6(6):869-76. DOI: 10.1093/hmg/6.6.869. View

10.

Dudeja V, Misra A, Pandey R, Devina G, Kumar G, Vikram N . BMI does not accurately predict overweight in Asian Indians in northern India. Br J Nutr. 2001; 86(1):105-12. DOI: 10.1079/bjn2001382. View

11.

BaHammam A, Obeidat A, Barataman K, Bahammam S, Olaish A, Sharif M . A comparison between the AASM 2012 and 2007 definitions for detecting hypopnea. Sleep Breath. 2014; 18(4):767-73. DOI: 10.1007/s11325-014-0939-3. View

12.

Bajaj S, Nigam P, Luthra A, Pandey R, Kondal D, Bhatt S . A case-control study on insulin resistance, metabolic co-variates & prediction score in non-alcoholic fatty liver disease. Indian J Med Res. 2009; 129(3):285-92. View

13.

Gami A, Caples S, Somers V . Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am. 2004; 32(4):869-94. DOI: 10.1016/s0889-8529(03)00069-0. View

14.

Foretz M, PACOT C, Dugail I, Lemarchand P, Guichard C, Le Liepvre X . ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol Cell Biol. 1999; 19(5):3760-8. PMC: 84202. DOI: 10.1128/MCB.19.5.3760. View

15.

Boston B . The hypothalamic path to obesity. J Pediatr Endocrinol Metab. 2004; 17 Suppl 4:1289-95. View

16.

Majmundar A, Wong W, Simon M . Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010; 40(2):294-309. PMC: 3143508. DOI: 10.1016/j.molcel.2010.09.022. View

17.

Jun J, Drager L, Najjar S, Gottlieb S, Brown C, Smith P . Effects of sleep apnea on nocturnal free fatty acids in subjects with heart failure. Sleep. 2011; 34(9):1207-13. PMC: 3157662. DOI: 10.5665/SLEEP.1240. View

18.

Li J, Bosch-Marce M, Nanayakkara A, Savransky V, Fried S, Semenza G . Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Physiol Genomics. 2006; 25(3):450-7. DOI: 10.1152/physiolgenomics.00293.2005. View

19.

Tilg H, Moschen A . Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010; 52(5):1836-46. DOI: 10.1002/hep.24001. View

20.

. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2002; 26 Suppl 1:S5-20. DOI: 10.2337/diacare.26.2007.s5. View