SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics.

BACKGROUND: The use of statins to lower high serum cholesterol levels may be associated with a number of adverse reactions, including severe myopathy. The solute carrier organic anion transporter 1B1 (SLCO1B1) gene, which encodes the organic anion-transporting polypeptide OATP1B1, is related to the intracellular transport of statins. The aim of this research was to study the association of rs2306283 and rs4149056 genetic polymorphism of the SLCO1B1 gene with the development of statin-induced myopathy in Jordanian diabetics receiving statins. METHODS: We included 413 patients attending the Diabetes Clinics of the National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan. The study was approved by the Institutional Review Board of NCDEG. Myopathy was defined as the elevation of creatine kinase more than 3 times the upper limit of normal. Every subject signed an informed consent form and donated 3-5 mL of venous blood. Genome DNA was extracted from lymphocytes of peripheral blood. Genotypes were identified using the Tetra Amplification Refractory Mutation System of SLCO1B1. RESULTS: The minor allele frequencies of rs2306283 [G] and rs4149056 [C] were 0.38 and 0.23, respectively. The two SNPs followed the Hardy-Weinberg equilibrium. The development of SIM was significantly associated with the homozygous and heterozygous minor allele genotype of rs4149056 (CC and CT), and the homozygous wild type allele genotype of rs2306283 (AA). There was no linkage disequilibrium between the two SNPs in the studied subgroups. CONCLUSION: Genetic polymorphism in the SLCO1B1 Gene is a risk factor for the development of SIM in Jordanian patients.

APOE Gene polymorphism among Jordanian Alzheimer`s patients with relation to lipid profile.

OBJECTIVE: To investigate the frequencies of the apolipoprotein E (APOE) alleles and genotypes and study their relationship with the lipid profile in Jordanian patients with late-onset Alzheimer`s disease (AD). METHODS: This case-control study was carried out on 71 Jordanian individuals: 38 patients with late-onset AD (age >/=65 years) and 33 age-matched healthy controls. All participants were recruited from senior homes and Jordan University Hospital, Amman, Jordan between January 2010 and December 2013. Each sample was examined for APOE`s 3 major isoforms (e2, e3, e4) using the polymerase chain reaction technique (PCR) followed by the sequencing technique. In addition, samples were screened for lipid profiles (total cholesterol (TC), high-density lipoprotein (HDL), lower-density lipoprotein (LDL), and triglyceride (TG) levels. RESULTS: The e3/e4 genotype and e4 allele prevalence were higher in AD patients compared to healthy controls (26.3% vs. 3.0%, p=0.03 and 15.8% vs. 4.5%, p=0.03; respectively). In the AD group, the e2 carriers showed the lowest levels of total and LDL cholesterol, and the e4 carriers showed the highest levels of total and LDL cholesterol, although the difference was not statistically significant (p>0.05). CONCLUSION: APOE-e4 frequency was almost 4 times higher in the AD group compared to the control group, and this difference was statistically significant. A trend that was observed in the AD group regarding the lipid profile and e2 and e4 carriers requires further investigation using a larger sample size.

Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach.

Autosomal recessive forms of Charcot-Marie-Tooth disease (ARCMT) are rare but severe disorders of the peripheral nervous system. Their molecular basis is poorly understood due to the extensive genetic and clinical heterogeneity, posing considerable challenges for patients, physicians, and researchers. We report on the genetic findings from a systematic study of a large collection of 174 independent ARCMT families. Initial sequencing of the three most common ARCMT genes (ganglioside-induced differentiation protein 1­GDAP1, SH3 domain and tetratricopeptide repeats-containing protein 2­SH3TC2, histidine-triad nucleotide binding protein 1­HINT1) identified pathogenic mutations in 41 patients. Subsequently, 87 selected nuclear families underwent single nucleotide polymorphism (SNP) genotyping and homozygosity mapping, followed by targeted screening of known ARCMT genes. This strategy provided molecular diagnosis to 22% of the families. Altogether, our unbiased genetic approach identified pathogenic mutations in ten ARCMT genes in a total of 41.3% patients. Apart from a newly described founder mutation in GDAP1, the majority of variants constitute private molecular defects. Since the gene testing was independent of the clinical phenotype of the patients, we identified mutations in patients with unusual or additional clinical features, extending the phenotypic spectrum of the SH3TC2 gene. Our study provides an overview of the ARCMT genetic landscape and proposes guidelines for tackling the genetic heterogeneity of this group of hereditary neuropathies.

Permanent neonatal diabetes mellitus in Jordan.

OBJECTIVE: Permanent neonatal diabetes mellitus (PNDM) is a rare heterogeneous form of diabetes that develops within the first 6 months of life. The objective of this study is to define the genetic etiology and incidence of permanent neonatal diabetes mellitus in Jordan. METHODS: This study was conducted in Jordan at the National Center of Diabetes, Endocrinology and Genetics, Amman, between 2006 and 2012. The study included 22 cases diagnosed with diabetes within the first year of life. RESULTS: The incidence of PNDM in Jordan was calculated as one case for every 203,221 live births. Mutations were found in six out of ten cases diagnosed before 6 months and included one homozygous ABCC8 p.R826W mutation, three cases with a heterozygous KCNJ11 p.R201C mutation, and two cases with a homozygous EIF2AK3 splicing mutation. CONCLUSION: The genetic etiology of PNDM in Jordan is different from that seen in European countries and more similar to other Arab countries.

Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan.

OBJECTIVE: To investigate the prevalence of thyroid dysfunction and autoimmunity in type 2 diabetic patients. METHODS: The study was conducted at the National Center for Diabetes, Endocrinology and Genetics, Jordan University Hospital, Amman, Jordan, between March 2000 and September 2000. A group of 908 type 2 diabetic patients (T2DM) were recruited in the study and underwent investigations for thyroid functions; free thyroxine (FT4), free tri-iodothyronine (FT3) and thyroid stimulating hormone (TSH). Six hundred had performed thyroid autoantibodies, thyroid peroxidase antibodies (TPOab) or antimicrosomal antibodies (AMA) and thyroglobulin antibodies (Tgab). They were compared with 304 non-diabetics, of those 282 had performed thyroid antibodies. RESULTS: Fifty-three (5.9%) of diabetic patients were known to have thyroid disease. As a direct result of screening, new thyroid disease cases were diagnosed in 6.6% of the patients. Thus, the overall prevalence of thyroid disease was found to be 12.5%. The most common was subclinical hypothyroidism (4.1%). In the control group, the prevalence of thyroid disease was 6.6%. The most common was subclinical hypothyroidism (5%). There was a significant difference between diabetics and control subjects p=0.0064. Positive TPOab was found in 8.3% of T2DM patients (N=600) versus 10.3% in the control group (N=282) p=0.412. Positivity for both TPOab and Tgab was found to be 2.5% of T2DM versus 6% of the control subjects p=0.0155. CONCLUSION: This study suggests that diabetic patients should be screened for asymptomatic thyroid dysfunction.

Antibodies to glutamic acid decarboxylase in Syrian and Jordanian type I diabetes patients and their siblings.

BACKGROUND: Attempts to identify the earliest events in the autoimmune process in type I diabetes mellitus suggests the glutamic acid decarboxylase (GAD) is one of the first and most important autoantigens. We conducted this study to determine the prevalence of antibodies to glutamic acid decarboxylase (anti-GAD) in both Syrian and Jordanian children with Type I diabetes and their siblings. PATIENTS AND METHODS: sera were obtained from 85 Syrian patients with type I diabetes (mean age 13.6 + 5.9 years), from 45 of their siblings (mean age 11 + 6.1 years), from 78 randomly selected Syrian control subjects (mean age 9.9 + 43 years), and from 95 Jordanian patients with type I diabetes (mean age 13.9 + 65 years), from 78 of their siblings (mean age 12.3 + 7.1 years), and from 100 randomly selected Jordanian control subjects (mean age 7.8 + 4.5 years). Sera were analyzed from anti-GAD using the enzyme linked immunosorbent assay (ELISA) technique. RESULTS: Prevalence of anti-GAD was 34.1% (29/85) in Syrian type I diabetes patients, 20% (9/45) in their siblings, 1.3% (1/78) in Syrian control subjects, 49.5% (47/95) in Jordanian type I diabetes patients, 23% (18/78) in their siblings, and 2% (2/100) in Jordanian control subjects. Differences between the Syrian and Jordanian type I diabetes groups and their siblings and controls were statistically significant. In patients with less than two years of diabetes duration, the frequency was 88.8% (16/18) for both groups. There was no correlation between sex and anti-GAD levels in their Syrian and Jordanian type I diabetes patients and their siblings. The positivity of anti-GAD tended to be more frequent at the age range of 5 to 8 years in siblings. Anti-GAD titers >90 ng/ml were found in 58.8% of type I diabetes patients and in 38% of siblings who were anti-GAD positive. CONCLUSION: Syria and Jordan have prevalence rates of anti-GAD among type I diabetes patients and their siblings that are among the highest reported in the world. Therefore, anti-GAD may be valuable as an early predictive marker for type I diabetes.