Variants of ESR1, APOE, LPL and IL-6 loci in young healthy subjects: association with lipid status and obesity

Findings BMI was increased (>25) in 22% of young healthy subjects. Increased cholesterol values (>5.0 mmol/L) were found in 23% of subjects, LDL-C (>3.0 mmol/L) in 23%, triglycerides (>1.7 mmol/L) in 11% of subjects. We found statistically significant differences in subjects' weight (p = 0.015), BMI (p = 0.023), and waist-hip ratio (WHR) (p = 0.015) in regard to their diet type; subjects with Mediterranean diet had the lowest values compared to those on continental and mixed diet. Significant associations were found for: LPL genetic polymorphic variant and abdominal obesity (p = 0.013), APO epsilon4 allele and hypercholesterolemia (p = 0.003), and ESR1-TA long allele and hypercholesterolemia (p = 0.011). ----- Background Human obesity is a multifactorial syndrome influenced also by genetic factors. Among gene variants found to be involved in body weight regulation and development of obesity, particular attention has been paid to polymorphisms in genes associated with obesity-related metabolic disorders. We explored the association of genetic polymorphisms of: estrogen receptor alpha (ESR1-TA repeats); interleukin-6 (IL-6 G-174C); apolipoprotein E (APO epsilon2, epsilon3, epsilon4); lipoprotein lipase Pvu II (LPL P+/-), with clinical variables: gender, age, body mass index (BMI), diet type and biological variables: triglycerides, cholesterol, HDL-C, LDL-C, CRP, homocysteine, urate, and glucose in 105 healthy young subjects (20-35 yrs) of Croatian origin. ----- Methods Genotyping of IL-6, LPL was performed by PCR-RFLP, of APOE by real-time PCR, and of ESR1 by PCR and capillary electrophoresis. Association analyses were performed of alleles and genotypes with biological variables. ----- Conclusion ESR-1, LPL, and APO E genetic polymorphic variants could represent predictive genetic risk markers for obesity-related metabolic disorders in young healthy subjects. Mediterranean type of diet is also an important protective factor against abdominal obesity

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

Initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction is related to platelet response to aspirin

INTRODUCTION: A proportion of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary angiography (PCI) presents with patent infarct-related artery (IRA) on initial angiography. We tested the hypothesis that stronger platelet response to aspirin in these patients at admission might be associated with higher initial coronary flow in the IRA. ----- METHODS: Platelet response to aspirin was assessed with Multiplate((R)) ASPI-test before coronary angiography in 70 patients on previous aspirin treatment admitted for acute STEMI. Coronary flow on initial angiogram was evaluated quantitatively according to the Thrombolysis in Myocardial Infarction (TIMI) grading system. Depending on the degree of arachidonic acid (AA) induced platelet aggregation in ASPI-test, patients were stratified into four quartiles and compared according to initial TIMI flow. ----- RESULTS: When TIMI flow was compared according to quartiles of platelet aggregation in ASPI-test, we have found significantly higher frequency of TIMI-2 and TIMI-3 flow among patients with low values of ASPI-test, i.e. with stronger aspirin response (P=0.014). None of the patients in the highest quartile of ASPI-test had TIMI flow of 2 or 3. ----- CONCLUSIONS: Patients with stronger antiplatelet response to aspirin therapy in acute STEMI are more likely to present with spontaneous IRA recanalization

Reconstructing the population history of European Romani from genome-wide data

The Romani, the largest European minority group with approximately 11 million people, constitute a mosaic of languages, religions, and lifestyles while sharing a distinct social heritage. Linguistic and genetic studies have located the Romani origins in the Indian subcontinent. However, a genome-wide perspective on Romani origins and population substructure, as well as a detailed reconstruction of their demographic history, has yet to be provided. Our analyses based on genome-wide data from 13 Romani groups collected across Europe suggest that the Romani diaspora constitutes a single initial founder population that originated in north/northwestern India 1.5 thousand years ago (kya). Our results further indicate that after a rapid migration with moderate gene flow from the Near or Middle East, the European spread of the Romani people was via the Balkans starting 0.9 kya. The strong population substructure and high levels of homozygosity we found in the European Romani are in line with genetic isolation as well as differential gene flow in time and space with non-Romani Europeans. Overall, our genome-wide study sheds new light on the origins and demographic history of European Romani