Hasil Pencarian  ::  Simpan CSV :: Kembali

"ABSTRAKGen CYP2C8 mempunyai beberapa alel mutan yang menyandi enzim CYP2C8 dengan kapasitas metabolisme yang rendah. Enzim CYP2C8 berperanan penting dalam metabolisme antimalaria amodiakuin menjadi metabolit aktifnya desetilamodiakuin sehingga mutasi pada gen CYP2C8 diduga berpotensi menyebabkan kegagalan terapi maupun kejadian efek samping agranulositosis yang dipicu oleh metabolit nonenzimatiknya amodiakuinkuinonimin.Penelitian observasional ini bertujuan untuk mengetahui frekuensi distribusi alel mutan gen CYP2C8 yaitu CYP2C8*2, CYP2C8*3, dan CYP2C8*4 pada salah satu kelompok etnik yang tinggal di daerah endemik malaria, yaitu suku Nias. Analisis PCR-RFLP untuk identifikasi alel gen CYP2C8 yang dilakukan pada 214 sampel berupa tetes darah di kertas saring (dot blot) dan subjek suku Nias memperlihatkan bahwa semua sampel membawa alel normal (wild type). Dengan tidak ditemukannya alel mutan gen CYP2C8 pada suku Nias, kita dapat berharap bahwa kemungkinan kegagalan terapi amodiakuin dan efek samping obat akibat metabolit nonenzimatiknya pada suku Nias tidak berkaitan dengan polimorfisme gen CYP2C8.

---

ABSTRACTThe CYP2C8 gene has been documented to have several alleles encoding enzyme with low metabolic capacity. Since CYP2C8 plays a major role in metabolizing antimalarial drug amodiaquine to its active metabolite desethylamodiaquine, it is assumed that mutation in CYP2C8 gene may potentially lead to treatment failure or to occurrence of adverse drug reactions such as agranulocytosis induced by its nonenzymatic metabolite amodiaquinequinoneimine.The aim of this study was to determine the frequency distribution of CYP2C8 mutant alleles particularly CYP2C8*2, CYP2C8*3 and CYP2C8*4 in one of the ethnic group that resides in malaria endemic area, Nias. PCR-RFLP analysis of 214 dot blot samples from Nias ethnic group subjects revealed that all of the samples carried the wild type allele of the CYP2C8 gene. In the absence of mutant alleles of CYP2C8 among Nias ethnic group, one can expect that treatment failure in amodiaquine therapy and adverse drug reactions associated with reactive metabolite of the drug are not related with CYP2C8 genetic polymorphisms."

"ABSTRAKLatar Belakang: Nefropati diabetik (ND) merupakan komplikasi mikrovaskular yang berkontribusi terhadap end stage renal disease (ESRD) pada penyandang DMT2. Polimorfisme gen apolipoprotein E (APOE) dihubungkan dengan dislipidemia merupakan faktor risiko untuk timbulnya ND.Tujuan: Mengetahui pengaruh polimorfisme gen APOE terhadap kejadian ND penyandang DMT2 di Palembang dan menganalisis pengaruh polimorfisme gen APOE terhadap perubahan profil lipid penyandang DMT2 dengan ND.Metode: Penelitian kasus kontrol pada penyandang DMT2 di Palembang. Kelompok kasus adalah penyandang DMT2 dengan ND dan kelompok kontrol adalah penyandang DMT2 tanpa ND yang memenuhi kriteria penyertaan.Hasil: Terdapat 37 penyandang DMT2 dengan ND (ACR > 300 mg/g kreatinin) dan 42 tanpa ND (ACR < 30 mg/g kreatinin). Tidak terdapat perbedaan bermakna pada usia, jenis kelamin, lama DM, tinggi badan, tekanan darah sistolik, glukosa darah puasa, HbA1c dan profil lipid. Terdapat perbedaan bermakna pada berat badan, IMT, TD diastolik, hemoglobin, ureum, kreatinin dan eGFR antara kasus dan kontrol. Distribusi genotip tidak berbeda bermakna. Pada kelompok kasus didapatkan peningkatan frekuensi alel gen APOE ε2 dibanding kontrol (62,2 % vs. 37,8 %). Dengan analisis bivariat didapatkan penyandang DMT2 yang mengandung alel gen APOE ε2 2,5 kali lipat dan bermakna (p = 0,023) dibandingkan gen APOE ε3 dalam menyebabkan ND sedangkan alel ε4 0,65 kali lipat dan tidak bermakna (p = 0,37). Profil lipid tidak berbeda bermakna baik pada penyandang DMT2 dengan ND maupun penyandang DMT2 tanpa nefropati.Simpulan: Frekuensi alel gen APOE ε2 lebih tinggi pada penyandang DMT2 dengan ND dibandingkan tanpa ND. Gen APOE ε2 merupakan faktor risiko kejadian ND pada penyandang DMT2. Tidak ada hubungan antara kejadian ND dengan perubahan profil lipid.

---

ABSTRACT

Backgrounds. Diabetic nephropathy is microvascular complication, largely contributed to end stage renal disease in T2DM patients. Apolipoprotein E (APOE) genetic polymorphism in association with dyslipidemia have been proposed as one of the risk factors for the development of diabetic nephropathy (DN).

Aim: To examine the effect of apolipoprotein E (APOE) gene polymorphism to DN incidence in patients with T2DM and to analyze the effect of APOE gene polymorphism to lipid profile in DN.

Method. Case control study at Palembang. Case group were T2DM with nephropathy and control group were T2DM without nephropathy.

Results. There were 37 patients with DN (ACR > 300 mg/g creatinine) and 42 patients without nephropathy (ACR < 30 mg/g creatinine). No significant differences in terms of age, sex, duration of DM, height, systolic blood pressure, fasting glucose, HbA1c and lipid profiles between the two groups. There were significant differences in weight, BMI, diastolic blood pressure, hemoglobine, ureum, creatinine and eGFR with p value 0.028, 0.013, 0.017, < 0.001, < 0.001, < 0.003 and < 0.002 respectively. The distribution of APOE genotypes between the two groups are the same. However, there was a significant difference in the allele frequencies, ε2 frequency was significantly higher in case group compared to control group (62.2 % vs. 37.8 %). On bivariate analysis ε2 allele showed 2.50 times to DN risk with p 0.023 while ε4 allele 0.65 times to DN risk. No significant difference in lipid profiles between DN and without nephropathy.

Conclusions. APOE ε2 allele was significantly higher in macroalbuminuria group. These result suggest that ε2 allele may be associated with the development of DN and ε2 allele was risk factor in T2DM patients. There were no correlation between APOE gene polymorphism and lipid profiles."

"Patogenesis nefropati diabetik (ND) merupakan hasil interaksi faktor hemodinamik, metabolik dan lingkungan serta faktor genetik. ND biasanya tidak terdeteksi secara klinis sampai terjadi kerusakan ginjal yang bermakna dapat berupa glomerulosklerosis, tubular atrofi dan fibrosis interstitial. KIM-1 dapat digunakan sebagai penanda adanya kerusakan tubulus ginjal. Hubungan polimorfisme gen ACE dengan nefropati diabetes masih tidak konsisten. Penelitian ini merupakan studi cross sectional komparasi antara dua kelompok penyandang DMT2 dengan atau tanpa nefropati yang bertujuan untuk mengetahui adanya kerusakan tubulus, polimorfisme gen ACE dan menganalisis hubungannya dengan kadar KIM-1 terhadap terjadinya kelainan tubulus. Didapatkan adanya peningkatan ekskresi KIM-1 urin pada 19 subjek pre-nefropati dengan median 1,3 (interquartile 1,5) ng/mL, 25 subjek nefropati insipien dengan median 1,6 (interquartile 2,3) ng/mL dan 12 subjek nefropati overt dengan rerata kadar KIM-1 3,1 ± 2,4 ng/mL. Terdapat polimorfisme gen ACE pada penyandang DMT2. Proporsi genotipe DD 9,3%, ID 33,3% dan II 57,4% pada kelompok NND, pada kelompok ND proporsi genotipe DD 4,7%, ID 34,1% dan genotipe II 61,2%. Dijumpai adanya hubungan bermakna antara alel D dengan peningkatan ekskresi KIM-1 urin pada kelompok pre-nefropati (p = 0,030). Peningkatan kadar KIM-1 urin pada kelompok pre-nefropati menunjukkan adanya kerusakan tubulus yang merupakan proses awal nefropati DM. Distribusi genotipe polimorfisme gen ACE pada penelitian ini menyerupai penelitian lain di negara-negara Asia, sedangkan di negara Eropa genotipe DD lebih banyak daripada genotipe II. Hubungan bermakna alel D dengan kadar KIM-1 hanya pada kelompok prenefropati mungkin disebabkan adanya faktor lain seperti kadar glukosa, kontrol glikemik, ureum, kreatinin dan kadar trigliserida yang memengaruhi. Simpulan: Terdapat peningkatan ekskresi KIM-1 urin pada penyandang DMT2 kelompok pre-nefropati yang meningkat secara bermakna pada penyandang DMT2 dengan nefropati overt. Peningkatan ekskresi KIM-1 urin dapat dipakai sebagai penanda kerusakan tubulus. Terdapat polimofisme gen ACE pada penyandang DMT2. Genotipe II lebih banyak dibanding genotipe ID dan DD. Dijumpai adanya hubungan alel D dengan peningkatan kadar KIM-1 urin pada penyandang DMT2 pre-nefropati.

---

The pathogenesis of nephropathy diabetic (ND) is the result of the interaction of haemodynamic, metabolic, environment, and genetic factors. In general, ND was clinically undetectable until kidney has been damaged significantly, in the form of glomerulosclerosis, tubular atrophy, or interstitial fibrosis. KIM-1 can be used as the initial indicator of kidney tubules damage. The relationship between ACE gene polymorphism and diabetic nephropathy was still inconsistent.

This research was a comparative cross-sectional study on two groups of DMT2 patients with and without nephropathy diabetic. The objectives of this study were to identify the tubules damage, ACE gene polymorphism, and to analyze the relationship between the degree of KIM-1 and the tubules damage. The increase of KIM-1 urine excretion was found in 19 pre-nephropathy subject (median = 1.3 with interquartile 1.5 ng/mL), in 25 incipient nephropathy subject (median = 1.6 (2.3) ng/mL), in 12 overt nephropathy subject (Mean = 3.1 ± 2,4 ng/mL). ACE polymorphism gene was found in DMT2 patients. In the NDD group, the genotype proportion of DD = 9.3%, ID = 33.3% and II = 57.4%. Whereas, in the ND group, the figures were 4.7%, 34.1% and 61.2%, respectively.

Significant relationship was found between allele D and the increase of KIM-1 urine on pre-nephropathy group (p = 0.030). The increase of KIM-1 urine on prenephropathy group shows the tubules damage which is the initial process of nephropathy diabetic. The genotype distribution of ACE gene polymorphism in this study was similar with the studies in Asian countries; however, in European countries the genotype DD is found higher than genotype II. The significant relationship between allele D and KIM-1 level in pre-nephropathy group might be the influence of other factors, such as glucose level, glycaemic control, urea, creatinine, and triglyceride level.

Conclusion: There was KIM-1 excretion increased on DMT2 pre-nephropathy group, which increase significantly in DMT2 overt nephropathy group. The increase of KIM-1 urine excretion can be used as the indicator of tubules damage. ACE gene polymorphism was found in DMT2 group, with genotype II was higher than genotype ID and DD. A significant relationship between allele D and the increase of KIM-1 urine excretion was found in pre-nephropathy group."

"Pendahuluan: Gen Interleukin 6 IL-6 merupakan gen yang mengkode protein sitokin yang menjaga homeostasis imun dan memainkan peran penting dalam inflamasi dan patogenesis berbagai penyakit. Dalam beberapa penelitian sebelumnya, polimorfisme pada promoter gen IL-6 dibuktikan memiliki hubungan bermakna dengan risiko terjadinya karsinoma sel skuamosa regio kepala dan leher. Tujuan: Mendeteksi polimorfisme gen IL-6 -174G/C pada penderita karsinoma sel skuamosa populasi Indonesia. Metode: Metode PCR-RFLP dilakukan pada 85 sampel penderita KSSKL dengan enzim restriksi Nla III yang divisualisasi dengan elektroforesis. Hasil: Polimorfisme gen IL-6 -174G/C ditemukan pada sampel yang diteliti sebesar 2.3. Kesimpulan: Polimorfisme genetik interleukin 6 meningkatkan risiko KSSKL di populasi Indonesia.

---

Introduction: Interleukin 6 IL 6 gene encodes a cytokine protein which maintains immune homeostasis and plays essential roles in inflammation and diseases rsquo pathogenesis. In previous studies, polymorphism of interleukin 6 gene promoter was found significantly associated with the head and neck squamous cell carcinoma risk.

Objectives: To detect the polymorphism of IL 6 174G C in Indonesian head and neck squamous cell carcinoma HNSCC patients.

Methods: PCR RFLP method was used to analyze 85 samples of HNSCC patients, using Nla III restriction enzyme and the results were visualized by electrophoresis.

Results: IL 6 174G C gene polymorphisms were found in the studied samples 2.3 .

Conclusion: IL 6 174G C gene polymorphisms increased the risk of HNSCC in Indonesian population."