Effect of SORT1 rs599839 Polymorphism on Lipid Profiles: A Single City Experience

Öz

Aim: The SORT1 gene encoding Sortilin-1 (SORT1), a receptor of the VPS10p family, is localized at 1p13.3. SORT1 has been associated with the risk of developing coronary heart disease (CHD) in genome wide association studies (GWAS) due to its association with hepatic lipid metabolism and low-density lipoprotein-cholesterol (LDL-C) levels. Various variations on the SORT1 gene region cause different effects on lipid profiles. Our aim in this study; To determine whether the SORT1 rs599839 gene variants have an effect on CHD development and lipid parameters in the Giresun province of Turkey.

Method: In this case-control study, the study group consisting of 396 men (209 KKH / 187 controls) was genotyped in terms of SORT1 rs599839 polymorphism using TaqMan 5 'Allelic Discrimination Test.

Results: There is no statistically significant difference between the patient and control groups in terms of SORT1 rs599839 genotypes (p=0.81). The presence of the G allele caused lower Total-C (p=0.005, p=0.032, respectively) and LDL-C (respectively; p=0.005, p=0.040) levels in both patient and control groups, while higher HDL-Cholesterol (p=0.001, p=0.006) levels were observed, respectively.

Conclusion: Our findings suggest that the SORT1 rs599839 polymorphism does not contribute directly to the pathogenesis of CHD. However, the presence of the minor G allele lowered Total-cholesterol and LDL-cholesterol levels and caused an increase in HDL-cholesterol levels. This situation gave the impression that the presence of the minor G allele has a positive effect on the lipid profile and is protective against CHD.

Anahtar Kelimeler

• SORT1
• Sortilin1
• polymorphism
• Coronary heart disease
• LDL-Cholesterol

SORT1 rs599839 Polimorfizminin Lipit Profillerine Olan Etkisi: Tek Şehir Deneyimi

Öz

Amaç: VPS10p ailesinin bir reseptörü olan Sortilin-1(SORT1)’i kodlayan SORT1 geni 1p13.3’de lokalizedir. SORT1 genom çapında ilişkilendirme çalışmalarında (GWAS) hepatik lipit metabolizması ve düşük dansiteli lipoprotein-kolesterol (LDL-K) seviyeleri ile olan ilişkisinden dolayı koroner kalp hastalığı (KKH) oluşturma riski ile ilişkilendirilmiştir. SORT1 gen bölgesi üzerindeki çeşitli varyasyonlar lipit profilleri üzerinde farklı etkilere neden olmaktadır. Bizim bu çalışmadaki amacımız; Giresun ilinde SORT1 rs599839 gen varyantlarının KKH gelişimi ve lipit parametreleri üzerine bir etkisinin olup olmadığını belirlemektir.

Yöntem: Bu vaka-kontrol çalışmasında 396 kişiden oluşan erkek çalışma grubunda (209 KKH /187 kontrol) SORT1 rs599839 polimorfizmi için TaqMan 5’ Allelik Ayrım Testi ile genotipleme yapıldı.

Bulgular: Hasta ve kontrol grupları arasında SORT1 rs599839 genotip dağılımları açısından istatistiksel olarak fark bulunmamaktadır (p=0.81). G allel varlığı hem hasta hem de kontrol grubunda daha düşük Total-Kolesterol (TK) (sırasıyla; p=0.005,p=0.032) ve LDL-K (sırasıyla; p=0.005,p=0.040) seviyelerine sebep olurken daha yüksek yüksek dansiteli lipoprotein-kolesterol (HDL-K) (sırasıyla; p=0.001,p=0.006) seviyeleri gözlenmiştir.

Sonuç: Bulgularımız SORT1 rs599839 polimorfizminin direk olarak KKH patogenezine katkısının olmadığı yönündedir. Ancak, minör G allel varlığının TK ve LDL-K seviyelerini düşürürken, HDL-K seviyelerinde yükselmeye sebep olduğu görülmüştür. Bu durum minör G allel varlığının lipit profili üzerine olumlu etki gösterdiği ve KKH’a karşı koruyucu olduğu izlenimini vermiştir.

Anahtar Kelimeler

• SORT1
• Sortilin1
• polimorfizm
• Koroner kalp hastalığı
• LDL-Kolesterol

Kaynakça

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