Tesis

Hubungan Antara Polimorfisme Gen FTO rs9939609 Dengan Obesitas; Kajian Khusus Terhadap Pola Asupan lemak = Association Between Polymorphism of FTO Gene (rs9939609) and Obesity With Emphasis on Fat Intake Pattern.

Obesitas merupakan masalah yang mengancam dunia karena prevalensinya semakin meningkat dari tahun ke tahun. Data dari Riset Kesehatan Dasar (Riskedas) 2013 menunjukkan prevalensi obesitas di Indonesia usia ≥18 tahun sebesar 15,4% dan kecenderungan pola diet tinggi lemak. Faktor genetik berperan 40-70% terhadap indeks massa tubuh (IMT). Salah satu gen yang diduga memengaruhi obesitas adalah gen FTO, dan variasi genetik terkuat adalah rs9939609 (subtitusi T/A). Variasi gen FTO rs9939609 dilaporkan menimbulkan ekspresi berlebihan dari gen FTO, yang akan memicu adipogenesis melalui demetilasi m 6 A yang berperan dalam alternatif splicing. Ekspresi berlebihan di hipotalamus juga memengaruhi pemilihan makanan densitas tinggi. Penelitian ini menggunakan pendekatan studi potong lintang komparatif yang bertujuan untuk melihat hubungan antara polimorfisme gen FTO rs9939609 dengan obesitas dan pola asupan lemak pada subyek dewasa di Indonesia. Pemeriksaan subyek dilakukan di Klinik Seruni, Departemen Gizi FKUI, yang terdiri dari 40 subyek non obes dan 40 subyek obes, usia 19-59 tahun, dan berdomisili di DKI Jakarta. Dilakukan pengukuran IMT, lingkar pinggang, massa lemak, persentase massa lemak, dan wawancara kuesioner FFQ semikuantitatif dan food recall 2x24 jam. Pemeriksaan variasi genetik gen FTO rs9939609 dilakukan dengan metode ARMS PCR. Rentang usia subyek 24-41 tahun. Riwayat keluarga dengan obesitas didominasi oleh kelompok obes. Indeks massa tubuh subyek penelitian berkisar 15,65 kg/m 2 2 –50,6 kg/m dengan lingkar pinggang pada kelompok obes melebihi batas normal. Massa lemak dan persentase massa lemak berasosiasi dengan IMT. Asupan total lemak melebihi nilai rekomendasi (27-42% dari total kalori) pada kedua kelompok. Pola asupan tinggi lemak banyak ditemui khususnya pada kelompok obes. Pada penelitian ini didapatkan distribusi genotipe berada pada kesetimbangan HardyWeinberg p=0,72 dengan MAF untuk variasi gen FTO rs9939609 di DKI Jakarta adalah 0,19. Subyek dengan genotipe AT/AA memiliki risiko obesitas 1,39x (p=0,009) dan pola asupan tinggi lemak 1,73x (p=0,011) lebih tinggi dibandingkan dengan genotipe TT. Subyek obes dengan genotipe AT/AA memiliki kecenderungan pola diet tinggi lemak 0,714x lebih tinggi dibandingkan dengan genotipe TT. Kesimpulan: Subyek dengan FTO rs9939609 genotipe AT/AA memiliki risiko obesitas yang lebih tinggi dan cenderung memilih makanan tinggi lemak dibandingkan dengan subyek genotipe TT.
Kata kunci : Polimorfisme, Gen FTO rs9939609, obesitas, pola asupan lemak


Obesity is a global health problem including in Indonesia. Baseline Health Research (Riskesdas) data showed that in 2013, the prevalence of obesity in Indonesia for adults aged ≥18 was 15.4% and tended to have high dietary fat intake (24-36% of daily total energy intake). Available data demonstrated that genetic factors are associated with BMI (40-70%). The FTO gene has been well documented as one of the genes to be associated with obesity by modulating adipogenesis with alternative splicing through m 6 A demethylation. FTO gene variation rs9939609 (T/A subtitution) was reported to lead to FTO mRNA overexpression in hypothalamus, which induce a preference towards high energy-dense foods. However, the correlation between FTO gene variation rs9939609 and fat intake pattern is still not well described. This study aimed to investigate the relationship between FTO gene (rs9939609) with obesity and fat intake pattern of Indonesian adults. A cross sectional comparative study design was applied in this study by recruiting 40 non obese and 40 obese subjects, aged 19-59, who were living in DKI Jakarta. The study was conducted at Seruni Clinic, Department of Nutrition, Universitas Indonesia. Measurements included BMI, waist circumference, fat mass, fat mass percentage, and interview with FFQ semiquantitative and food recall 2x24 questionaire. Genetic variation was determine by ARMS PCR. Results showed the age range was 24-41 years and the family history of obesity is more prevalent in the obese group. Body mass index ranged between 15,65 kg/m 2 2 -50,65 kg/m with waist circumference in obese group was above normal limit. High fat mass and fat mass percentage related to BMI. Dietary fat intake was above the recommended value in both groups (total fat 27-42% of total daily energy intake). However, the proportion of people with high fat intake in the obese group were higher than the non-obese group. The genotype distribution of FTO gene (rs9939609) was at Hardy-Weinberg equilibrium (p= 0.72) with MAF of 0.19 in DKI Jakarta. This study showed that the AT/AA genotype has 1.39x higher risk of obesity (p= 0.009) and 1.73x higher dietary fat intake (p= 0.011) than the TT genotype. Obese subjects with AT/AA genotype tended to have higher dietary fat intake of 0.714x than the obese subjects with TT genotype. These findings suggest that subjects with the AT/AA genotype of the FTO rs9939609 have higher obesity risk and preference to high dietary fat intake than subjects with the TT genotype.
Keywords : Polymorphism, FTO gene rs9939609, obesity,dietary fat intake