Pro12Ala polymorphism in the PPARG gene is not assocIated wIth the development of insulIin resistance and type 2 diabetes in the Turkish population: A case-control study

Year 2021, Volume: 31 Issue: 4, 339 - 343, 15.12.2021

Dudu Erkoç Kaya , Hilal Arikoglu , Funda İşçioğlu , Suleyman Ipekci , Süleyman Baldane

https://doi.org/10.54005/geneltip.1017082

Abstract

Objective: Type 2 diabetes (T2D) is the most common type of diabetes and has become a serious public health problem in our country as worldwide. Reduction of insulin secretion and/or insulin resistance (IR) development are two major defects in T2D pathogenesis. PPARG2, which is encoded by the peroxisome proliferator activated receptor gamma (PPARG) gene, located chromosome 3p25, is mainly expressed in adipocytes and regulates a large number of key genes involved in regulation of glucose and lipid metabolism. The first reported candidate gene associated with T2D is PPARG2 (Pro12Ala variant), due to its functional importance. We aimed to evaluate the effects of Pro12Ala on IR development and T2D risk in 650 individuals, which of 387 (181 non-obese/ 206 obese) individuals with T2D and 264 (137 nonobese/127 obese) healthy individuals in Konya region.
Method: T2D-related biochemical parameters were analyzed from blood samples and HOMA-IR (HOMA index) was calculated. Individuals with a HOMAIR index higher than 2.5 were considered resistant to insulin. Pro12Ala genotyping was performed by RT-PCR technique in DNA samples isolated from lymphocytes. P<0.05 was considered statistically significant.
Results: Patient and control groups except Obese patient group were not in HardyWeinberg equilibrium (p<0.05). Pro12Ala polymorphism had no effect on T2D risk and biochemical parameters according to association analysis under dominant, recessive, additive models (p>0.05).
Conclusion: Consequently, the Pro12Ala in PPARG gene was not associated with T2D and biochemical phenotypes in the Turkish population. The polygenic nature of the disease and complexity of environmental factors makes it difficult to understand the effect of the genes in the pathogenesis of T2D. Further studies in larger populations are needed to reveal the possible role of PPARG in the genetic background of the disease. The study is the first report of PPARG and T2D association Turkish.

Keywords

Type 2 diabetes, PPARG, Pro12Ala, Turkish population

Project Number

213S035

PPARG genindeki Pro12Ala polimorfizmi, Türk populasyonunda insülin direnci ve tip 2 diyabet ile ilişkili değildir: Bir vaka-kontrol çalışması

Abstract

Amaç: Tip 2 diyabet (T2D), diyabetin en sık görülen türüdür ve tüm dünyada olduğu gibi ülkemizde de ciddi bir halk sağlığı sorunu haline gelmiştir. İnsülin sekresyonunun azalması ve/veya insülin direnci (İR) gelişimi, T2D patogenezinde yer alan iki ana bozukluktur. Kromozom 3p25'te yer alan peroksizom proliferatör aktive reseptör gama (PPARG) geni tarafından kodlanan ve esas olarak adipositlerde eksprese edilen PPARG2, glikoz ve lipid metabolizmasının düzenlenmesinde yer alan çok sayıda anahtar geni düzenler. Fonksiyonel önemi dolayısıyla, T2D gelişimi ile ilişkisi ilk rapor edilen aday gen PPARG2 (Pro12Ala varyantı)’dir. Çalışmamızda, PPARG genindeki Pro12Ala'nın IR gelişimi ve T2D riski üzerine etkilerini Konya bölgesinde yaşayan 387 (181 non-obez/ 206 obez) T2D ve 264 (137 non-obez/127 obez) sağlıklı birey olmak üzere toplam 650 kişide değerlendirmeyi amaçladık.
Yöntem: Bireylerden alınan kan örneklerinden, T2D ilişkili biyokimyasal parametreler analiz edildi ve sonrasında HOMA-IR (HOMA indeksi) hesaplandı. HOMAIR indeksi 2.5'ten yüksek olan kişiler insüline dirençli olarak kabul edildi. İzole edilen DNA örneklerinde, Pro12Ala genotiplendirmesi RT-PCR tekniği ile yapıldı. İstatistiksel analiz için SPSS18.0 programı kullanıldı. P<0.05 istatistiksel olarak anlamlı kabul edildi.
Bulgular: Obez hasta grubu dışında diğer hasta ve ve kontrol grupları Hardy-Weinberg dengesinde değildi (p<0.05). Dominant, resesif ve aditif modeller kurularak yapılan ilişkilendirme analizine göre Pro12Ala polimorfizminin T2D riski ve ilişkili biyokimyasal parametreler üzerine bir etkisi bulunmadı (p>0.05).
Sonuç: Hastalığın poligenik doğası ve çevresel faktörlerin karmaşıklığı, genlerin T2D patogenezindeki etkisinin anlaşılmasını zorlaştırmaktadır. Bu nedenle, PPARG'nin hastalığın genetik zeminindeki olası rolünü ortaya çıkarmak için daha büyük popülasyonlarda daha fazla çalışmaya ihtiyaç vardır. Çalışma Türk toplumunda PPARG ve T2D ilişkisi bakımından sunulan ilk rapordur.

Keywords

Tip 2 diyabet, PPARG, Pro12Ala, Türk populasyonu

Supporting Institution

TÜBİTAK

Project Number

213S035

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