Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Tip II Diabetes Mellituslu Hastalarda Apo B İçeren Lipoproteinlerdeki Sialik Asidin Önemi

Tez (Tıpta Uzmanlık) -- Kırıkkale Üniversitesi48234

The importance of sialic acid at lipoproteins containing APO B in patients with type 2 diabetes mellitus

YÖK Tez ID: 156923ÖZET Karaca Kara F, Tip II Diabetes Mellituslu Hastalarda Apo B İçeren Lipoproteinlerdeki Sialik Asidin Önemi, Kırıkkale Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı Uzmanlık Tezi, Kırıkkale, 2004. Diabetes mellitusta (DM) kardiovasküler hastalıktan ölüm riski normal populasyondan beş kat daha fazladır. Çalışmaların bir kısmında düşük dansiteli lipoproteinlerdeki (LDL) düşük sialik asit (S A) içeriği aterojenite ve koroner arter hastalığı ile ilişkili bulunmuştur. Bundan dolayı DM'de kardiovasküler risk yönünden serum proteinlerindeki ve Apo B içeren lipoproteinlerdeki SA seviyelerini ölçüp, çeşitli parametrelerle olan ilişkisini araştırdık. Bu çalışmada 96 Tip II DM'li ve 25 kişilik kontrol grubunda, Apo B içeren lipoproteinlerdeki sialik asidi (Bağlı SA: BSA), total sialik asit (TSA), açlık kan şekeri (AKŞ), trigliserid (TG), total kolesterol, total protein (TPROT), yüksek dansiteli lipoprotein (HDL-K), Apo B ve HbAıc ölçümleri yapıldı. TSA/PROT, BSA/Apo B, BSA/ Apo B içeren lipoproteinlerdeki kolesterol (BSA / ALT-K), TSA/BSA, BSA/LDL ve BSA/TG'de hesaplandı. Diabetik grupta AKŞ, TG ve HbAıc düzeylerinin anlamlı ölçüde yüksek (p< 0,001), BSA/TG değerinin ise düşük olduğu (p=0,014) tespit edildi. Hasta ve kontrol grubunda BSA ile; TSA (r=0,477 p<0,001; r=0.525 p=0,007), TG ( r=0,631 p<0,001; r=0,686 p<0,001), kolesterol (r=0,615 p<0,001; r=0,767 p<0,001) ve LDL- K arasında (r=0,353 p<0,001; r=0,694 p<0,001) anlamlı bir pozitif korelasyon bulunurken, hasta grubunda ise HDL-K ile anlamlı negatif bir korelasyon (r=-0,367 p<0,001) bulundu. Hasta grubunda AKŞ ile TSA arasında, TSA ile hasta yaşı arasında ve HbAıc ile TSA/PROT arasında anlamlı pozitif korelasyon saptandı. BSA/TG değerlerinin, diabetik grupta kontrol grubundan daha düşük olması, açlık kanında TG düzeyinin ana kaynağı olan VLDL'nin SA içeriğinin düşük olduğunu düşündürmektedir. Düşük SA içeriği VLDL'nin daha fazla LDL'ye dönüşümüne neden olmaktadır. Bu nedenle, tesbit ettiğimiz BSA/TG düzeyindeki düşüklüğün diabetiklerdeki ateroskleroz patogenezinde rol oynayabileceğine inanıyoruz. Anahtar Kelimeler: Sialik asit, diabetes mellitus, lipoproteinler.VI ABSTRACT Karaca Kara F, The Importance of Sialic Acid at Lipoproteins Containing Apo B in Patients with Type II Diabetes Mellitus, University of Kirikkale, Faculty of Medicine, Departman of Biochemistry, Specialization Thesis, Kirikkale, 2003. It has been suggested that the risk of death from coroner artery heart disease (CAHD) in diabetic patients is five times higher than normal population. Several researchers have reported relation between sialic acid (SA) content of LDL and atherosclerosis and CAHD. For this reason, we investigated SA levels of sera proteins and lipoproteins containing ApoB, we also investigated relationship between SA levels and several parameters. Samples were obtained from 96 type II diabetic and 25 control subjects. Sialic acid in lipoproteins containing Apo B (Bound SA: BSA), total serum sialic acid (TSA), fasting glucose (FG), trigliserid (TG), total kolesterol, total protein, high density lipoprotein cholesterol (HDL-C), Apo B and HbAic levels were measured and TSA/TPROT, BSA /ApoB, BSA/Cholesterol in Lipoproteins Containing Apo B (BSA/C-LpApo B), TSA/BSA, BSA/Low Density Lipoproteins Cholesterol (BSA/LDL-C), BSA/TG were calculated in these patients and results were compared to those of controls, who were chosen among healthy subjects. Results suggested that, FG,TG and HbAic levels are significantly higher (p<0,001) but BSA/TG ratio is lower (p=0,014) in diabetic patients compared to nondiabetics. In study and control groups, significant positive corelations were found between BSA and TSA, (r=0,477 p<0,001; r=0,525 p=0,007), TG ( r=0,631 p<0,001; r=0,686 p<0,001), cholesterol (r=0,615 p<0,001; r=0,767 p<0,001) and LDL-C level (r=0,353 p<0,001; r=0,694 p<0,001) but in the study group significant negative correlation was found between BSA and HDL-C levels (r=-0,367 p<0,001). There were also significant positive correlations between FG and TSA, TSA and age of patients, HbAic and TSA/PROT in the patient group. The BSA/TG ratio is decreased in the diabetic group. This lower level of this ratio suggest that S A content of the VLDL the major source of the fasting blood TG level is decreased. Decreased SA content leads to increased transformation of VLDL to LDL, so wevıı believe that decreased BSA/TG ratio may have a role in pathogenesis of diabetic atherosclerosis. Keywords: Sialic acid, diabetes mellitus, lipoprotein

The effects of the non-volatile anaesthetic agents, propofol and thiopental, on erythrocyte sedimentation rate

WOS: 000253452100006PubMed: 18484074Objectives. The reduction of erythrocyte sedimentation rate (ESR) induced by general anaesthesia was demonstrated in our previous study. The purpose of the present study was to investigate whether the type of induction agent (propofol or thiopental) used for general anaesthesia had any effects on ESR. Methods. Sixty-four patients (ASA Physical Status Classification, I-II) scheduled for elective surgery under general anaesthesia were randomly assigned into two groups. In Group I, propofol and in Group II, thiopental were used as induction agents. Two blood samples were obtained before induction and 10 minutes after endotracheal intubation for ESR measurements. Results. The ESR values of the second samples from both groups were significantly lower than the values of the first samples, but there were no statistically significant differences in ESR values between the values of the two groups. Conclusion. The results showed that general anaesthesia decreased ESR values regardless of the type of agents being used for induction of anaesthesia. The reason might be related to other drugs used in both groups, or to a common effector mechanism of the two induction agents. The underlying mechanism needs to be investigated

The decrease in erythrocyte sedimentation rate related to general anesthesia

WOS: 000242381600004PubMed: 17148844The aim of this study was to investigate whether general anesthetic agents change erythrocyte sedimentation rate (ESR) affecting erythrocytes' shape and membrane structure in routine clinical dose manner. Forty patients (23 female and 17 male) undergoing elective surgery were included to the study. Blood samples were obtained just before induction of the anesthesia and 10 minutes after endotracheal intubation. The ESR was measured using Test-1 ESR analyzer. ESR values of the second blood samples were significantly lower than the first values (p < 0.001). At the beginning, the ESR was 18.1 +/- 11.5 mm/h, and then it decreased to 13.1 +/- 9.3 at 10th minutes. Our results indicated that anesthetic agents affected the ESR. No increase was observed in the second ESR values which were equal to, or less than the first values. General anesthesia may lead to this decrease changing electrolyte balance of erythrocyte, affecting ligands of agglomerins in membrane directly and indirectly, or changing discoid shape of erythrocyte