Yazun Jarrar, Sara Abudahab, Ghasaq Abdul-Wahab, Dana Zaiter, Abdalla Madani, Sara J Abaalkhail, Dina Abulebdah, Hussam Alhawari, Rami Musleh, Su-Jun Lee
{"title":"Ⅱ型糖尿病NAT2基因变异及脂质调节的临床意义。","authors":"Yazun Jarrar, Sara Abudahab, Ghasaq Abdul-Wahab, Dana Zaiter, Abdalla Madani, Sara J Abaalkhail, Dina Abulebdah, Hussam Alhawari, Rami Musleh, Su-Jun Lee","doi":"10.2147/PGPM.S422495","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in <i>NAT2</i> can influence the enzyme's activity and potentially lead to the development of certain diseases.</p><p><strong>Aim: </strong>This study aimed to investigate the association of <i>NAT2</i> variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients.</p><p><strong>Methods: </strong>We sequenced the whole protein-coding region in <i>NAT2</i> using Sanger's method among a sample of 45 Jordanian T2DM patients and 50 control subjects. Moreover, we analyzed the lipid profiles of the patients and examined any potential associations with <i>NAT2</i> variants.</p><p><strong>Results: </strong>This study revealed that the heterozygous <i>NAT2*13 C/T</i> genotype is significantly (<i>P</i> = 0.03) more common among T2DM (44%) than non-T2DM subjects (23.5%). Furthermore, the frequency of homozygous <i>NAT2*13 T/T</i> genotype was found to be significantly higher (<i>P</i> = 0.03) among T2DM patients (26.7%) compared to that of non-T2DM subjects (11%). The heterozygous <i>NAT2*7 G/A</i> genotype was exclusively observed in T2DM patients (11.1%) and absent in the control non-T2DM group. Moreover, among T2DM patients, those with a homozygous <i>NAT2*11</i> T/T genotype exhibited significantly higher levels of triglycerides (381.50 ± 9.19 ng/dL) with a <i>P</i> value of 0.01 compared to those with heterozygous <i>NAT2*11</i> C/T (136.23 ± 51.12 ng/dL) or wild-type <i>NAT2*11</i> C/C (193.65 ± 109.89 ng/dL) genotypes. T2DM patients with homozygous <i>NAT2*12</i> G/G genotype had a significantly (<i>P</i> = 0.04) higher triglyceride levels (275.67 ± 183.42 ng/dL) than the heterozygous <i>NAT2*12 A/G</i> (140.02 ± 49.53 ng/dL) and the wild <i>NAT2*12 A/A</i> (193.65 ± 109.89 ng/dL).</p><p><strong>Conclusion: </strong>The finding in this study suggests that the <i>NAT2</i> gene is a potential biomarker for the development of T2DM and changes in triglyceride levels among Jordanians. However, it is important to note that our sample size was limited; therefore, further clinical studies with a larger cohort are necessary to validate these findings.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/be/pgpm-16-847.PMC10505377.pdf","citationCount":"0","resultStr":"{\"title\":\"Clinical Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.\",\"authors\":\"Yazun Jarrar, Sara Abudahab, Ghasaq Abdul-Wahab, Dana Zaiter, Abdalla Madani, Sara J Abaalkhail, Dina Abulebdah, Hussam Alhawari, Rami Musleh, Su-Jun Lee\",\"doi\":\"10.2147/PGPM.S422495\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in <i>NAT2</i> can influence the enzyme's activity and potentially lead to the development of certain diseases.</p><p><strong>Aim: </strong>This study aimed to investigate the association of <i>NAT2</i> variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients.</p><p><strong>Methods: </strong>We sequenced the whole protein-coding region in <i>NAT2</i> using Sanger's method among a sample of 45 Jordanian T2DM patients and 50 control subjects. Moreover, we analyzed the lipid profiles of the patients and examined any potential associations with <i>NAT2</i> variants.</p><p><strong>Results: </strong>This study revealed that the heterozygous <i>NAT2*13 C/T</i> genotype is significantly (<i>P</i> = 0.03) more common among T2DM (44%) than non-T2DM subjects (23.5%). Furthermore, the frequency of homozygous <i>NAT2*13 T/T</i> genotype was found to be significantly higher (<i>P</i> = 0.03) among T2DM patients (26.7%) compared to that of non-T2DM subjects (11%). The heterozygous <i>NAT2*7 G/A</i> genotype was exclusively observed in T2DM patients (11.1%) and absent in the control non-T2DM group. Moreover, among T2DM patients, those with a homozygous <i>NAT2*11</i> T/T genotype exhibited significantly higher levels of triglycerides (381.50 ± 9.19 ng/dL) with a <i>P</i> value of 0.01 compared to those with heterozygous <i>NAT2*11</i> C/T (136.23 ± 51.12 ng/dL) or wild-type <i>NAT2*11</i> C/C (193.65 ± 109.89 ng/dL) genotypes. T2DM patients with homozygous <i>NAT2*12</i> G/G genotype had a significantly (<i>P</i> = 0.04) higher triglyceride levels (275.67 ± 183.42 ng/dL) than the heterozygous <i>NAT2*12 A/G</i> (140.02 ± 49.53 ng/dL) and the wild <i>NAT2*12 A/A</i> (193.65 ± 109.89 ng/dL).</p><p><strong>Conclusion: </strong>The finding in this study suggests that the <i>NAT2</i> gene is a potential biomarker for the development of T2DM and changes in triglyceride levels among Jordanians. However, it is important to note that our sample size was limited; therefore, further clinical studies with a larger cohort are necessary to validate these findings.</p>\",\"PeriodicalId\":56015,\"journal\":{\"name\":\"Pharmacogenomics & Personalized Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/be/pgpm-16-847.PMC10505377.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics & Personalized Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/PGPM.S422495\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics & Personalized Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/PGPM.S422495","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Clinical Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.
Background: N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in NAT2 can influence the enzyme's activity and potentially lead to the development of certain diseases.
Aim: This study aimed to investigate the association of NAT2 variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients.
Methods: We sequenced the whole protein-coding region in NAT2 using Sanger's method among a sample of 45 Jordanian T2DM patients and 50 control subjects. Moreover, we analyzed the lipid profiles of the patients and examined any potential associations with NAT2 variants.
Results: This study revealed that the heterozygous NAT2*13 C/T genotype is significantly (P = 0.03) more common among T2DM (44%) than non-T2DM subjects (23.5%). Furthermore, the frequency of homozygous NAT2*13 T/T genotype was found to be significantly higher (P = 0.03) among T2DM patients (26.7%) compared to that of non-T2DM subjects (11%). The heterozygous NAT2*7 G/A genotype was exclusively observed in T2DM patients (11.1%) and absent in the control non-T2DM group. Moreover, among T2DM patients, those with a homozygous NAT2*11 T/T genotype exhibited significantly higher levels of triglycerides (381.50 ± 9.19 ng/dL) with a P value of 0.01 compared to those with heterozygous NAT2*11 C/T (136.23 ± 51.12 ng/dL) or wild-type NAT2*11 C/C (193.65 ± 109.89 ng/dL) genotypes. T2DM patients with homozygous NAT2*12 G/G genotype had a significantly (P = 0.04) higher triglyceride levels (275.67 ± 183.42 ng/dL) than the heterozygous NAT2*12 A/G (140.02 ± 49.53 ng/dL) and the wild NAT2*12 A/A (193.65 ± 109.89 ng/dL).
Conclusion: The finding in this study suggests that the NAT2 gene is a potential biomarker for the development of T2DM and changes in triglyceride levels among Jordanians. However, it is important to note that our sample size was limited; therefore, further clinical studies with a larger cohort are necessary to validate these findings.
期刊介绍：
Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability.
In particular, emphasis will be given to:
Genomic and proteomic profiling
Genetics and drug metabolism
Targeted drug identification and discovery
Optimizing drug selection & dosage based on patient''s genetic profile
Drug related morbidity & mortality intervention
Advanced disease screening and targeted therapeutic intervention
Genetic based vaccine development
Patient satisfaction and preference
Health economic evaluations
Practical and organizational issues in the development and implementation of personalized medicine programs.
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