POLIMORFISME E23K GEN POTASSIUM INWARDLY RECTIFYING CHANNEL SUB FAMILY J MEMBER 11 (KCNJ11) DAN SEKRESI INSULIN PADA INDIVIDU DENGAN RIWAYAT KELUARGA DIABETES MELITUS TIPE 2

Sunita RS, dr. Ahmad Hamim Sadewa, Ph.D.

2015 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Diabetes melitus tipe 2 (DMT2) merupakan penyakit multifaktorial yang melibatkan faktor genetik dan lingkungan. Gen potassium inwardly-rectifying chanel sub family J member 11 (KCNJ11)merupakan gen penyusun kanal ion K+ yang sensitif terhadap ATP (kanal KATP) dan berperan penting dalam sekresi insulin.Polimorfisme E23K gen KCNJ11merupakan faktor risikoDMT2. Individu pembawa alel A dengan riwayat keluarga DMT2 berisiko menderita DMT2. Tujuan Penelitian: Penelitian ini bertujuan mengetahui polimorfisme E23K gen KCNJ11 dan sekresi insulin pada individu dengan riwayat keluarga DMT2 (kasus) dan tanpa riwayat keluarga DMT2 (kontrol). Metode: Penelitian ini merupakanpenelitian kasus kontrol. Subyek penelitian adalah 34 kasus dan 34 kontrol. Kadar glukosa darah puasa (GDP) dianalisis dengan spektrofotometri, kadar insulin puasa dengan ELISA dan polimorfisme E23K gen KCNJ11dengan polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Nilai Homeostatic model asessment β (HOMA-β) diperoleh dari pemeriksaan kadar insulin puasa dan kadar GDP. Data dianalisis dengan Independen Sampel T-test,Mann-WhitneyU-test, Chi-Square test danOne- Way ANOVAdengan nilai p<0,05 sebagai batas signifikansi. Hasil: Frekuensi genotip AA pada kasus lebih tinggi daripada kontrol (41% dan6%) (p=0,001).Frekuensi alel A pada kasus lebih tinggi daripada kontrol (68%dan 38%)(p=0,001). Risiko untuk mendapatkan alel A 3,38 kali lebih tinggi pada kasusdaripadakontrol (p=0,001, OR 3,38, CI 95% 1,67-6,84).Nilai HOMA-β individu dengan genotip AA (85,44% ± 39,55) lebih rendah daripada genotip GA (212,20% ± 79,30) dan GG (254,00% ± 61,98) pada subyek penelitian (p=0,000). Kesimpulan: Individu dengan riwayat keluarga DMT2 mempunyai risiko lebih tinggi untuk mendapatkan alel A dibandingkan individu tanpa riwayat keluarga DMT2. Nilai HOMA-β individu dengan genotip AAlebih rendah daripada genotip GAdan GG pada penelitian ini. Kata kunci:

Background: Type 2Diabetes Mellitus (T2DM) is a multifactorial disease involves both genetic and environment factors. Potassium inwardly-rectifying chanel sub family J member 11 (KCNJ11) gene which is an ATP sensitivepotassium channel contributes in insulin secretion. The E23K polymorphism in KCNJ11 gene has been known as one of risk factor of T2DM. Moreover, individualswith A allele and family history ofT2DM have higher risk of T2DM. Objectives: This research was aimed to investigate E23K polymorphism in KCNJ11 gene and insulin secretion between individualswith and without family history of T2DM. Method: This research was a case-control study involved 34 casesand 34 controls. Fasting blood glucose was analyzed using spectrophotometry, fasting blood insulin level was measured by ELISA, while E23K polymorphism of KCNJ11 was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Homeostatic model assessment β (HOMA-β) level was determined using fasting blood glucose level and fasting blood insulin level. All the data obtained were statically analyzed using Independent Sample T-test, Mann-Whitney U-test, Chi-Square test, and One-Way ANOVA withp value <0.05 considered as significant difference. Result: Frequency of AA genotype in individualswith family history of T2DMwere higher than in individualswithout family history of T2DM (41% and 6%; respectively) (p=0.001). Frequency of A allele in individualswith family history of T2DM were higher than in individualswithout family history of T2DM (68% and 38%; respectively) (p=0.001). The risk of A allele in individualswith family history of T2DM were 3 times higher than in individualswithout family history of T2DM (p=0.001, OR 3.34, CI 95% 1.67-6.84). HOMA-β value in AA genotype (85.44% ± 39.55) were lower than that in GA (212.20% ±79.30) and GG (254.00%± 61.98) genotypes(p=0.000). Conclusion: The risk of having A allele in individualswith family history of T2DM were higher than that in individualswithout family history of T2DM. HOMA-β value in AA genotype were lower than that in GA and GG genotypes.

Kata Kunci : DMT2, polimorfisme E23K gen KCNJ11, HOMA-β