CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration

In developed countries, age-related macular degeneration is a common cause of blindness in the elderly. A common polymorphism, encoding the sequence variation Y402H in complement factor H (CFH), has been strongly associated with disease susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than the Y402H variant. Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of four common haplotypes (of which two were associated with disease susceptibility and two seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). Our results suggest that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility

Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2.

PURPOSE: To report a novel mouse model of achromatopsia with a cpfl3 mutation found in the ALS/LtJ strain. METHODS: The effects of a cpfl3 mutation were documented using fundus photography, electroretinography (ERG), and histopathology. Genetic analysis was performed using linkage studies and PCR gene identification. RESULTS: Homozygous cpfl3 mice had poor cone-mediated responses on ERG at 3 weeks that became undetectable by 9 months. Rod-mediated waveforms were initially normal, but declined with age. Microscopy of the retinas revealed progressive vacuolization of the photoreceptor outer segments. Immunocytochemistry with cone-specific markers showed progressive loss of labeling for alpha-transducin, but the cone outer segments in the oldest mice examined remained intact and positive with peanut agglutinin (PNA). The cpfl3 mapped to mouse chromosome 3 at the same location as human GNAT2, known to cause achromatopsia. Sequence analysis revealed a missense mutation due to a single base pair substitution in exon 6 in cpfl3. CONCLUSIONS: The Gnat2(cpfl3) mutation leads to cone dysfunction and the progressive loss of cone alpha-transducin immunolabeling. Despite a poor cone ERG signal and loss of cone alpha-transducin label, the cones survive at 14 weeks as demonstrated by PNA staining. This mouse model of achromatopsia will be useful in the study of the development, pathophysiology, and treatment of achromatopsia and other cone degenerations. The gene symbol for the cpfl3 mutation has been changed to Gnat2(cpfl3)

Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study)

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro-and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity. (c) 2019 The Author(s) Published by S. Karger AG, BaselC1 [Sonmez, Alper; Haymana, Cem; Demirci, Ibrahim] Univ Hlth Sci, Gulhane Sch Med, Dept Endocrinol & Metab, TR-06018 Ankara, Turkey.[Yumuk, Volkan] Istanbul Univ, Cerrahpasa Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Barcin, Cem] Univ Hlth Sci, Gulhane Sch Med, Dept Cardiol, Ankara, Turkey.[Kiyici, Sinem] Univ Hlth Sci, Bursa Yuksek Ihtisas Training & Res Hosp, Dept Endocrinol & Metab, Bursa, Turkey.[Guldiken, Sibel] Trakya Univ, Med Fac, Dept Endocrinol & Metab, Edirne, Turkey.[Oruk, Gonca] Izmir Katip Celebi Univ, Ataturk Educ & Res Hosp, Dept Endocrinol & Metab, Izmir, Turkey.[Saydam, Basak Ozgen] Dokuz Eylul Univ, Med Fac, Dept Endocrinol & Metab, Izmir, Turkey.[Baldane, Suleyman] Selcuk Univ, Med Fac, Dept Endocrinol & Metab, Konya, Turkey.[Kutluturk, Faruk] Gaziosmanpasa Univ, Med Fac, Dept Endocrinol & Metab, Tokat, Turkey.[Kucukler, Ferit Kerim] Hitit Univ, Med Fac, Dept Endocrinol & Metab, Corum, Turkey.[Deyneli, Oguzhan] Marmara Univ, Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Cetinarslan, Berrin] Kocaeli Univ, Med Fac, Dept Endocrinol & Metab, Kocaeli, Turkey.[Sabuncu, Tevfik] Harran Univ, Med Fac, Dept Endocrinol & Metab, Urfa, Turkey.[Bayram, Fahri] Erciyes Univ, Med Fac, Dept Endocrinol & Metab, Kayseri, Turkey.[Satman, Ilhan] Istanbul Univ, Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Ayturk, Semra] Trakya Univ, Sch Med, Dept Endocrinol & Metab, Edirne, Turkey.[Yilmaz, Murat] Corlu REYAP Private Hosp, Dept Endocrinol & Metab, Corlu, Turkey.[Asik, Mehmet] Canakkale 18 March Univ, Sch Med, Dept Endocrinol & Metab, Canakkale, Turkey.[Dinccag, Nevin; Cakmak, Ramazan; Turker, Fulya; Idiz, Cemile; Hacisahinogullari, Hulya; Bagdemir, Elif; Yildiz, Busra; Haliloglu, Ozlem] Istanbul Univ, Sch Med, Dept Endocrinol & Metab, Cerrahpasa, Turkey.[Sancak, Seda] Univ Hlth Sci, Sch Med, Fatih Sultan Mehmet Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Ozsari, Levent; Cagiltay, Eylem] Univ Hlth Sci, Sch Med, Sultanabdulhamit Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Imre, Eren] Marmara Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Sait Gonen; Boysan, S. Nur] Istanbul Sci Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Altuntas, Yuksel; Ozturk, Feyza Yener] Univ Hlth Sci, Sch Med, Sisli Hamidiye Etfal Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Mert, Meral; Piskinpasa, Hamide] Univ Hlth Sci, Istanbul Bakirkoy Dr Sadi Konuk Training & Res Ho, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Aydin, Hasan] Yeditepe Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Ersoy, Canan; Oz Gul, Ozen] Uludag Univ, Sch Med, Dept Endocrinol & Metab, Bursa, Turkey.[Selek, Alev] Kocaeli Univ, Sch Med, Dept Endocrinol & Metab, Kocaeli, Turkey.[Dogru, Teoman; Kirik, Ali] Balikesir Univ, Sch Med, Dept Internal Med, Balikesir, Turkey.[Kebapci, Nur; Efe, Belgin] Eskisehir Osmangazi Univ, Sch Med, Dept Endocrinol & Metab, Odunpazari Eskisehir, Turkey.[Kaya, Ahmet; Cordan, Ilker] Necmettin Erbakan Univ, Sch Med, Dept Endocrinol & Metab, Konya, Turkey.[Kirac, Cem Onur] Selcuk Univ, Sch Med, Dept Endocrinol & Metab, Konya, Turkey.[Capa, Zehra] Univ Hlth Sci, Gulhane Sch Med, Ankara, Turkey.[Capa, Zehra] Gulhane Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Cesur, Mustafa] Private Guven Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Yetkin, Ilhan] Gazi Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Corapcioglu, Demet; Canlar, Sule] Ankara Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Yildiz, Okan Bulent; Sendur, Suleyman Nahit] Hacettepe Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Cakir, Bekir; Ozdemir, Didem] Yildirim Beyazit Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Corakci, Ahmet] Ufuk Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Kutlu, Mustafa] Private Bayindir Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Bascil Tutuncu, Neslihan; Bozkus, Yusuf] Baskent Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Cakal, Erman] Univ Hlth Sci, Sch Med, Diskapi Yildirim Beyazit Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Demirbas, Berrin] TOBB Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Ertek, Sibel] Private Mem Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Altay, Mustafa; Dagdeviren, Murat] Univ Hlth Sci, Sch Med, Kecioren Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Abedi, Amir Hassein] Erciyes Univ, Sch Med, Dept Endocrinol & Metab, Kayseri, Turkey.[Cetinkalp, Sevki; Ozisik, Hatice] Ege Univ, Sch Med, Dept Endocrinol & Metab, Izmir, Turkey.[Yener, Serkan] Dokuz Eylul Univ, Sch Med, Dept Endocrinol & Metab, Izmir, Turkey.[Guney, Engin; Unubol, Mustafa] Adnan Menderes Univ, Sch Med, Dept Endocrinol & Metab, Aydin, Turkey.[Yaylali, Guzin Fidan; Topsakal, Senay] Pamukkale Univ, Sch Med, Dept Endocrinol & Metab, Denizli, Turkey.[Hekimsoy, Zeliha] Celal Bayar Univ, Sch Med, Dept Endocrinol & Metab, Manisa, Turkey.[Akbaba, Gulhan] Mugla Univ, Sch Med, Dept Endocrinol & Metab, Mugla, Turkey.[Aslan, Ibrahim] Univ Hlth Sci, Antalya Training & Res Hosp, Sch Med, Dept Endocrinol & Metab, Antalya, Turkey.[Balci, Mustafa Kemal; Dalkiran, Sefika] Akdeniz Univ, Sch Med, Dept Endocrinol & Metab, Antalya, Turkey.[Akbay, Esen] Mersin Univ, Sch Med, Dept Endocrinol & Metab, Mersin, Turkey.[Gul, Kamile] Kahramanmaras Sutcu Imam Univ, Sch Med, Dept Endocrinol & Metab, Kahramanmaras, Turkey.[Agbaht, Kemal] Private Defne Hosp, Dept Endocrinol & Metab, Antalya, Turkey.[Yilmaz, Muge Ozsan] Mustafa Kemal Univ, Sch Med, Dept Endocrinol & Metab, Antakya, Turkey.[Bozkirli, Emre] Baskent Univ, Adana Training Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Tetiker, B. Tamer; Cetinkaya Altuntas, Seher] Cukurova Univ, Sch Med, Dept Endocrinol & Metab, Adana, Turkey.[Atmaca, Aysegul; Durmus, Elif Tutku] 19 Mayis Univ, Sch Med, Dept Endocrinol & Metab, Samsun, Turkey.[Mete, Turkan] Univ Hlth Sci, Sch Med, Samsun Training & Res Hosp, Dept Endocrinol & Metab, Samsun, Turkey.[Dikbas, Oguz] Giresun Univ, Sch Med, Dept Endocrinol & Metab, Giresun, Turkey.[Akin, Safak] Recep Tayyip Erdogan Univ, Sch Med, Dept Endocrinol & Metab, Rize, Turkey.[Nuhoglu, Irfan; Ersoz, Halil Onder] Karadeniz Tech Univ, Sch Med, Dept Endocrinol & Metab, Trabzon, Turkey.[Bayraktaroglu, Taner] Bulent Ecevit Univ, Sch Med, Dept Endocrinol & Metab, Zonguldak, Turkey.[Sisman, Pinar] Kars Harakani State Hosp, Dept Endocrinol & Metab, Kars, Turkey.[Sahin, Ibrahim; Cetin, Sedat] Inonu Univ, Sch Med, Dept Endocrinol & Metab, Malatya, Turkey.[Capoglu, Ilyas; Akbas, Emin Murat] Erzincan Univ, Sch Med, Dept Endocrinol & Metab, Erzincan, Turkey.[Ucler, Rifki] Yuzuncu Yil Univ, Sch Med, Dept Endocrinol & Metab, Van, Turkey.[Eren, Mehmet Ali] Harran Univ, Sch Med, Dept Endocrinol & Metab, Sanliurfa, Turkey.[Tuzcu, Alpaslan Kemal; Pekkolay, Zafer] Dicle Univ, Sch Med, Dept Endocrinol & Metab, Diyarbakir, Turkey.[Ozkaya, Mesut] Univ Hlth Sci, Sch Med, Gaziantep Ersin Arslan Res & Training Hosp, Gaziantep, Turkey.[Araz, Mustafa] Gaziantep Univ, Sch Med, Dept Endocrinol & Metab, Gaziantep, Turkey.[Salman, Serpil] Liv Hosp Ulus, Dept Endocrinol & Metab, Istanbul, Turkey.[Dizdar, Oguzhan Sitki] Kayseri Educ & Res Hosp, Dept Internal Med, Kayseri, Turkey.[Gurkan, Eren] Mustafa Kemal Univ, Dept Endocrinol & Metab, Antakya, Turkey.[Kargili Carlioglu, Ayse] Erzurum Reg Educ & Res Hosp, Dept Endocrinol & Metab, Erzurum, Turkey

Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with Diabetes mellitus (TEMD study)

AIMS: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus. METHODS: A nationwide, multicenter survey consecutively enrolled patients who were under follow up for at least a year. Optimal control was defined as HbA1c < 7%, home arterial blood pressure (ABP) < 135/85 mmHg, or LDL-C < 100 mg/dL. Achieving all parameters indicated triple metabolic control. RESULTS: HbA1c levels of patients (n = 5211) were 8.6 ± 1.9% (71 ± 22 mmol/mol) and 7.7 ± 1.7% (61 ± 19 mmol/mol), in Type 1 and Type 2 diabetes, respectively. Glycemic control was achieved in 15.3% and 40.2%, and triple metabolic control was achieved in 5.5% and 10.1%, respectively. Only 1.5% of patients met all the criteria of being non-obese, non-smoker, exercising, and under triple metabolic control. Low education level was a significant predictor of poor glycemic control in both groups. CONCLUSIONS: Few patients with Type 2, and even fewer with Type 1 diabetes have optimal metabolic control in Turkey. TEMD study will provide evidence-based information to policy makers to focus more on the quality and sustainability of diabetes care in order to reduce the national burden of the disease

The genetic history of the Southern Arc. A bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra-West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the IndoAnatolian language family was in West Asia, with only secondary dispersals of non-Anatolian IndoEuropeans from the steppe