Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study

English version

Autoři: Christian Obirikorang ^aff001; Emmanuel Acheampong ^aff001; Lawrence Quaye ^aff003; Joseph Yorke ^aff004; Ernestine Kubi Amos-Abanyie ^aff005; Priscilla Abena Akyaw ^aff005; Enoch Odame Anto ^aff001; Simon Bannison Bani ^aff003; Evans Adu Asamoah ^aff001; Emmanuella Nsenbah Batu ^aff001
Působiště autorů: Department of Molecular Medicine, School of Medical Science, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana ^aff001; School of Medical and Health Science, Edith Cowan University, Joondalup, Australia ^aff002; School of Allied Health Sciences, University of Development Studies, Tamale, Ghana ^aff003; Department of Surgery, Komfo Anokye Teaching Hospital, Kumasi, Ghana ^aff004; H3Africa Kidney Disease Research Project, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana ^aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227779

Souhrn

Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06–6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3–88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6–493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.

Klíčová slova:

Antiretroviral therapy – Ghana – HIV – Cholesterol – Lipids – Lipoproteins – Variant genotypes

Zdroje

1. Piot P, Bartos M, Ghys PD, Walker N, Schwartländer B: The global impact of HIV/AIDS. Nature 2001, 410(6831):968. doi: 10.1038/35073639 11309626

2. Global AIDS Update 2017; July 2017. UNAIDS. AIDSinfo website; accessed July 2017,

3. Bor J, Herbst AJ, Newell M-L, Bärnighausen TJS: Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment. 2013, 339(6122):961–965.

4. May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S, et al.: Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. 2014, 28(8):1193.

5. Patterson S, Cescon A, Samji H, Chan K, Zhang W, Raboud J, et al.: Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada. 2015, 15(1):274.

6. Feeney ER, Mallon PW: HIV and HAART-associated dyslipidemia. The open cardiovascular medicine journal 2011, 5:49. doi: 10.2174/1874192401105010049 21643501

7. Dubé MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, et al: Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clinical Infectious Diseases 2003, 37(5):613–627. doi: 10.1086/378131 12942391

8. Estrada V, Portilla J: Dyslipidemia related to antiretroviral therapy. AIDS reviews 2011, 13(1):49–56. 21412389

9. Obirikorang C, Quaye L, Osei-Yeboah J, Odame EA, Asare I: Prevalence of metabolic syndrome among HIV-infected patients in Ghana: A cross-sectional study. Nigerian medical journal: journal of the Nigeria Medical Association 2016, 57(2):86.

10. Ngala R, Fianko K: Dyslipidaemia and dysglycaemia in HIV-infected patients on highly active anti-retroviral therapy in Kumasi Metropolis. African health sciences 2013, 13(4):1107–1116. doi: 10.4314/ahs.v13i4.35 24940339

11. Ankrah DN, Lartey M, Mantel-Teeuwisse AK, Leufkens HG: Five-year trends in treatment changes in an adult cohort of HIV/AIDS patients in Ghana: a retrospective cohort study. BMC infectious diseases 2017, 17(1):664. doi: 10.1186/s12879-017-2752-7 28969591

12. Fisher SD, Miller TL, Lipshultz SE: Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis. Atherosclerosis 2006, 185(1):1–11. doi: 10.1016/j.atherosclerosis.2005.09.025 16297390

13. Umpleby AM, Das S, Stolinski M, Shojaee-Moradie F, Jackson NC, Jefferson W, et al.: Low density lipoprotein apolipoprotein B metabolism in treatment-naive HIV patients and patients on antiretroviral therapy. Antiviral therapy 2005, 10(5):663. 16152760

14. Fox J, Boffito M, Winston A: The clinical implications of antiretroviral pharmacogenomics. 2006.

15. Lazzaretti RK, Gasparotto AS, Sassi MGdM, Polanczyk CA, Kuhmmer R, Silveira JM,: Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART. The Scientific World Journal 2013, 2013.

16. Rios-Gonzalez BE, Luevano-Ortega KE, Saldana-Cruz AM, Gonzalez-Garcia JR, Magaña-Torres MT: Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. Journal of genetics 2013, 92(2):114–119.

17. Brown MS, Goldstein JL: A receptor-mediated pathway for cholesterol homeostasis. Science 1986, 232(4746):34–47. doi: 10.1126/science.3513311 3513311

18. de Almeida E, Simão A, Morimoto H, Kallaur A, Flauzino T, Alfieri D, de Oliveira J, et al.: Pvuii genetic polymorphism of low density lipoprotein receptorin human immunodeficiency virus type 1-infected patients: possible association with dyslipidemia. Journal of AIDS and Clinical Research 2014, 5(11).

19. Wang X, Guo H, Li Y, Wang H, He J, Mu L, et al: Interactions among genes involved in reverse cholesterol transport and in the response to environmental factors in dyslipidemia in subjects from the Xinjiang rural area. PloS one 2018, 13(5):e0196042. doi: 10.1371/journal.pone.0196042 29758034

20. Klos KL, Sing CF, Boerwinkle E, Hamon SC, Rea TJ, Clark A, et al.,: Consistent effects of genes involved in reverse cholesterol transport on plasma lipid and apolipoprotein levels in CARDIA participants. Arteriosclerosis, thrombosis, and vascular biology 2006, 26(8):1828–1836. doi: 10.1161/01.ATV.0000231523.19199.45 16763159

21. Chen SN, Cilingiroglu M, Todd J, Lombardi R, Willerson JT, Gotto AM, et al.,: Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis. BMC medical genetics 2009, 10(1):111.

22. Chien K-L, Hsu H-C, Chen Y-C, Su T-C, Lee Y-T, Chen M-F: Association between sequence variant of c. 553 G> T in the apolipoprotein A5 gene and metabolic syndrome, insulin resistance, and carotid atherosclerosis. Translational Research 2009, 154(3):133–141. doi: 10.1016/j.trsl.2009.06.005 19665689

23. Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, et al.,: A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008, 322(5908):1702–1705. doi: 10.1126/science.1161524 19074352

24. Aragonès G, Alonso-Villaverde C, Pardo-Reche P, Rull A, Beltrán-Debón R, Rodríguez-Gallego E, et al.,: Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism. BMC medical genetics 2011, 12(1):120.

25. Vardarlı AT, Harman E, Çetintaş VB, Kayıkçıoğlu M, Vardarlı E, Zengi A, et al: Polymorphisms of lipid metabolism enzyme-coding genes in patients with diabetic dyslipidemia. Anatolian journal of cardiology 2017, 17(4):313. doi: 10.14744/AnatolJCardiol.2016.7142 28315561

26. Chang M-h, Yesupriya A, Ned RM, Mueller PW, Dowling NF: Genetic variants associated with fasting blood lipids in the US population: Third National Health and Nutrition Examination Survey. BMC medical genetics 2010, 11(1):62.

27. Lazzaretti RK, Gasparotto AS, Sassi MGdM, Polanczyk CA, Kuhmmer R, Silveira JM, et al.,: Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART. 2013, 2013.

28. Kodogo V, Zhou DT, Oektedalen O, Duri K, Stray-Pedersen B, et al.,: Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. 2016, 10:190.

29. Nock NL, Pillai ALC: Dyslipidemia: genetics and role in the metabolic syndrome. In: Dyslipidemia-From Prevention to Treatment. edn.: InTech; 2012.

30. Kodogo V, Zhou DT, Oektedalen O, Duri K, Stray-Pedersen B, Gomo E: Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. The open AIDS journal 2016, 10:190. doi: 10.2174/1874613601610010190 27790293

31. Expert Panel on Detection E: Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Jama 2001, 285(19):2486. doi: 10.1001/jama.285.19.2486 11368702

32. Agongo G, Nonterah EA, Debpuur C, Amenga-Etego L, Ali S, Oduro A, et al.: The burden of dyslipidaemia and factors associated with lipid levels among adults in rural northern Ghana: An AWI-Gen sub-study. PloS one 2018, 13(11):e0206326. doi: 10.1371/journal.pone.0206326 30485283

33. Xu C, Bai R, Zhang D, Li Z, Zhu H, Lai M, et al.,: Effects of APOA5− 1131T> C (rs662799) on Fasting Plasma Lipids and Risk of Metabolic Syndrome: Evidence from a Case-Control Study in China and a Meta-Analysis. PloS one 2013, 8(2):e56216. doi: 10.1371/journal.pone.0056216 23468858

34. Tsai MY, Ordovas JM, Li N, Straka RJ, Hanson NQ, Arends VL, et,: Effect of fenofibrate therapy and ABCA1 polymorphisms on high-density lipoprotein subclasses in the Genetics of Lipid Lowering Drugs and Diet Network. Molecular genetics and metabolism 2010, 100(2):118–122. doi: 10.1016/j.ymgme.2010.03.001 20346718

35. Fairoozy RH, White J, Palmen J, Kalea AZ, Humphries SE: Identification of the functional variant (s) that explain the low-density lipoprotein receptor (LDLR) GWAS SNP rs6511720 association with lower LDL-C and risk of CHD. PloS one 2016, 11(12):e0167676. doi: 10.1371/journal.pone.0167676 27973560

36. Kc R, Srivastava A, Wilkowski J, Richter C, Shavit J, Burke D, et al.,: Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection. Scientific reports 2016, 6:32048. doi: 10.1038/srep32048 27557703

37. Anastos K, Lu D, Shi Q, Tien PC, Kaplan RC, Hessol NA, et al.,: Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens. JAIDS Journal of Acquired Immune Deficiency Syndromes 2007, 45(1):34–42. doi: 10.1097/QAI.0b013e318042d5fe 17460470

38. El‐Sadr W, Mullin C, Carr A, Gibert C, Rappoport C, Visnegarwala F, et al.,: Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral‐naïve cohort. HIV medicine 2005, 6(2):114–121. doi: 10.1111/j.1468-1293.2005.00273.x 15807717

39. Limas TGd, Pinto GdA, Marcato LM, Coelho DR: Analysis of the prevalence of dyslipidemia in individuals with HIV and its association with antiretroviral therapy. Revista da Sociedade Brasileira de Medicina Tropical 2014, 47(5):547–551.

40. Tadewos A, Addis Z, Ambachew H, Banerjee S: Prevalence of dyslipidemia among HIV-infected patients using first-line highly active antiretroviral therapy in Southern Ethiopia: a cross-sectional comparative group study. AIDS research and therapy 2012, 9(1):31. doi: 10.1186/1742-6405-9-31 23095661

41. Kotler DP: HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients. JAIDS Journal of Acquired Immune Deficiency Syndromes 2008, 49:S79–S85. doi: 10.1097/QAI.0b013e318186519c 18725816

42. Panse I, Vasseur E, Raffin‐Sanson M, Staroz F, Rouveix E, Saiag P: Lipodystrophy associated with protease inhibitors. British Journal of Dermatology 2000, 142(3):496–500. doi: 10.1046/j.1365-2133.2000.03363.x 10735957

43. Echevarria KL, Hardin TC, Smith JA: Hyperlipidemia associated with protease inhibitor therapy. Annals of Pharmacotherapy 1999, 33(7–8):859–863. doi: 10.1345/aph.18174 10466916

44. Behrens G, Dejam A, Schmidt H, Balks H-J, Brabant G, et al.,: Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. Aids 1999, 13(10):F63–F70. doi: 10.1097/00002030-199907090-00001 10416516

45. Manfredi R, Chiodo F: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate. Journal of Infection 2001, 42(3):181–188. doi: 10.1053/jinf.2001.0829 11545549

46. Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, et al.,: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature genetics 2009, 41(1):47. doi: 10.1038/ng.269 19060911

47. Rotger M, Bayard C, Taffé P, Martinez R, Cavassini M, Bernasconi E, et al.,: Contribution of genome-wide significant single-nucleotide polymorphisms and antiretroviral therapy to dyslipidemia in HIV-infected individuals: a longitudinal study. Circulation: Cardiovascular Genetics 2009, 2(6):621–628.

48. Wang N, Tall AR: Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arteriosclerosis, thrombosis, and vascular biology 2003, 23(7):1178–1184. doi: 10.1161/01.ATV.0000075912.83860.26 12738681

49. Von Eckardstein A, Nofer J-R, Assmann G: High density lipoproteins and arteriosclerosis: role of cholesterol efflux and reverse cholesterol transport. Arteriosclerosis, thrombosis, and vascular biology 2001, 21(1):13–27. doi: 10.1161/01.atv.21.1.13 11145929

50. Jong MC, Hofker MH, Havekes LM: Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arteriosclerosis, thrombosis, and vascular biology 1999, 19(3):472–484. doi: 10.1161/01.atv.19.3.472 10073946

51. Šeda O, Šedová L: New apolipoprotein AV: comparative genomics meets metabolism. Physiol Res 2003, 52:141–146. 12678656

52. Lai C-Q, Tai E-S, Tan CE, Cutter J, Chew SK, et al.,: The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. Journal of lipid research 2003, 44(12):2365–2373. doi: 10.1194/jlr.M300251-JLR200 12951359

53. Echeverria P, Guardiola M, González M, Vallvé JC, Bonjoch A, et al.,: Association between polymorphisms in genes involved in lipid metabolism and immunological status in chronically HIV-infected patients. Antiviral research 2015, 114:48–52. doi: 10.1016/j.antiviral.2014.12.002 25500319

54. Asiedu GB, Myers-Bowman KS: Gender differences in the experiences of HIV/AIDS-related stigma: A qualitative study in Ghana. Health care for women international 2014, 35(7–9):703–727. doi: 10.1080/07399332.2014.895367 24564483

Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study

Souhrn

Klíčová slova:

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