Measurement of Absolute Copy Number Variation of Glutathione S-Transferase M1 Gene by Digital Droplet PCR and Association Analysis in Tunisian Rheumatoid Arthritis Population

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2017 Jul 14

PMID 28703442

Citations 3

Authors

Yosser Achour

Mohamed Sahbi Ben Kilani

Mariem Ben Hamad

Sameh Marzouk

Nadia Mahfoudh

Zouheir Bahloul

Leila Keskes

Elisabeth Petit-Teixeira

Abdellatif Maalej

Affiliations

Soon will be listed here.

Abstract

Background: The investigation of copy number variations (CNVs) analysis of candidate genes is currently an important research area in modulating human diseases. We aimed to quantify CNVs in glutathione S-transferase M1 (GSTM1) gene and determine its genetic contribution in Tunisian rheumatoid arthritis (RA) and its subsets through an innovative technique for quantification.

Methods: A total of 165 RA cases and 102 healthy controls were included in the study. Using a recently powerful approach of digital droplet PCR (ddPCR), we quantified GSTM1 gene to determine the presence of no, one, or multiple copy number (CN) at high levels of sensitivity and specificity. Odds ratio and Fisher exact test were performed to estimate the association risk for GSTM1CNVs in RA.

Results: Copy number identified by ddPCR was 0, 1, and 2 copies per diploid genome. A high frequency of '0' copy was revealed with 54% in RA patients. The deletion ('0' copy) of GSTM1 was found to be a significant risk factor for anti-cyclic citrullinated peptide (anti-CCP) positive RA (OR=4.16, CI =[1.17-14.7]). In addition, a lack of association was found when comparing between the CNVs of RA patients and those of controls.

Conclusion: This study highlights the powerful accuracy of ddPCR for the quantification of CNVs and suggests that the variation in the CN of GSTM1 is associated with anti-CCP positivity in RA. However, it does not indicate a specific role in the susceptibility to the disease in our Tunisian sample.

Citing Articles

Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies.

Li P, Li S, Zheng P Rheumatol Ther. 2024; 11(2):239-256.

PMID: 38376734 PMC: 10920578. DOI: 10.1007/s40744-023-00634-1.

An Update Evolving View of Copy Number Variations in Autoimmune Diseases.

Song R, Gao C, Zhao J, Zhang J Front Genet. 2022; 12:794348.

PMID: 35126462 PMC: 8810490. DOI: 10.3389/fgene.2021.794348.

Measurement of absolute copy number variation of Glutathione S-Transferase M1 gene by digital droplet PCR and association analysis in Tunisian Rheumatoid Arthritis population.

Achour Y, Ben Kilani M, Ben Hamad M, Marzouk S, Mahfoudh N, Bahloul Z J Clin Lab Anal. 2017; 32(3).

PMID: 28703442 PMC: 6816960. DOI: 10.1002/jcla.22300.

References

Stahl E, Raychaudhuri S, Remmers E, Xie G, Eyre S, Thomson B . Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010; 42(6):508-14. PMC: 4243840. DOI: 10.1038/ng.582. View

Huggett J, Foy C, Benes V, Emslie K, Garson J, Haynes R . The digital MIQE guidelines: Minimum Information for Publication of Quantitative Digital PCR Experiments. Clin Chem. 2013; 59(6):892-902. DOI: 10.1373/clinchem.2013.206375. View

Bekris L, Shephard C, Peterson M, Hoehna J, Van Yserloo B, Rutledge E . Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity. 2006; 38(8):567-75. DOI: 10.1080/08916930500407238. View

Criswell L, Saag K, Mikuls T, Cerhan J, Merlino L, Lum R . Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women. Ann Rheum Dis. 2006; 65(9):1163-7. PMC: 1798304. DOI: 10.1136/ard.2005.049676. View

Weaver S, Dube S, Mir A, Qin J, Sun G, Ramakrishnan R . Taking qPCR to a higher level: Analysis of CNV reveals the power of high throughput qPCR to enhance quantitative resolution. Methods. 2010; 50(4):271-6. DOI: 10.1016/j.ymeth.2010.01.003. View

Achour Y, Ben Kilani M, Ben Hamad M, Marzouk S, Mahfoudh N, Bahloul Z . Measurement of absolute copy number variation of Glutathione S-Transferase M1 gene by digital droplet PCR and association analysis in Tunisian Rheumatoid Arthritis population. J Clin Lab Anal. 2017; 32(3). PMC: 6816960. DOI: 10.1002/jcla.22300. View

Norskov M, Frikke-Schmidt R, Loft S, Tybjaerg-Hansen A . High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals. Clin Biochem. 2008; 42(3):201-9. DOI: 10.1016/j.clinbiochem.2008.10.020. View

Fahmi H, Pelletier J, Martel-Pelletier J . PPARgamma ligands as modulators of inflammatory and catabolic responses in arthritis. An overview. J Rheumatol. 2002; 29(1):3-14. View

Xu S, Wang Y, Roe B, Pearson W . Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1 deletion. J Biol Chem. 1998; 273(6):3517-27. DOI: 10.1074/jbc.273.6.3517. View

10.

Wiencke J, Wrensch M, Miike R, Zuo Z, Kelsey K . Population-based study of glutathione S-transferase mu gene deletion in adult glioma cases and controls. Carcinogenesis. 1997; 18(7):1431-3. DOI: 10.1093/carcin/18.7.1431. View

11.

MacGregor A, Snieder H, Rigby A, Koskenvuo M, Kaprio J, Aho K . Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000; 43(1):30-7. DOI: 10.1002/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B. View

12.

Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P . A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991; 11(3):298-300, 302. View

13.

Grabar P, Logar D, Tomsic M, Rozman B, Dolzan V . Genetic polymorphisms of glutathione S-transferases and disease activity of rheumatoid arthritis. Clin Exp Rheumatol. 2009; 27(2):229-36. View

14.

Blackburn A, Matthaei K, Lim C, Taylor M, Cappello J, Hayes J . Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways. Mol Pharmacol. 2005; 69(2):650-7. DOI: 10.1124/mol.105.018911. View

15.

Geisler S, Olshan A . GSTM1, GSTT1, and the risk of squamous cell carcinoma of the head and neck: a mini-HuGE review. Am J Epidemiol. 2001; 154(2):95-105. DOI: 10.1093/aje/154.2.95. View

16.

Mikuls T, LeVan T, Gould K, Yu F, Thiele G, Bynote K . Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans. Arthritis Rheum. 2011; 64(3):655-64. PMC: 3272109. DOI: 10.1002/art.33408. View

17.

Song G, Bae S, Lee Y . The glutathione S-transferase M1 and P1 polymorphisms and rheumatoid arthritis: a meta-analysis. Mol Biol Rep. 2012; 39(12):10739-45. DOI: 10.1007/s11033-012-1965-5. View

18.

Urayama K, Thompson P, Taylor M, Trachtenberg E, Chokkalingam A . Genetic variation in the extended major histocompatibility complex and susceptibility to childhood acute lymphoblastic leukemia: a review of the evidence. Front Oncol. 2013; 3:300. PMC: 3859964. DOI: 10.3389/fonc.2013.00300. View

19.

McInnes I, Schett G . The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23):2205-19. DOI: 10.1056/NEJMra1004965. View

20.

Costenbader K, Feskanich D, Mandl L, Karlson E . Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006; 119(6):503.e1-9. DOI: 10.1016/j.amjmed.2005.09.053. View