Consanguinity, endogamy and inborn errors of metabolism in Oman: a cross-sectional study.

The Sultanate of Oman, like many other Arab countries, has relatively high rates of consanguinity. Reports suggest that the incidence of inborn errors of metabolism (IEM) is also high in Oman. This retrospective cross-sectional study was designed to evaluate the number of patients with IEM being followed at the only two tertiary centers in Oman treating such patients, and to calculate the consanguinity rates among these families. The electronic medical records of all patients were reviewed for demographic and clinical characteristics. A total of 285 patients with IEM were being followed at the 2 centers involved; 162 (56.8%) were male and 123 (43.2%) were female. The history of consanguinity was documented or available for 241 patients: 229 patients (95%) were born to consanguineous parents related as second cousins or closer. First-cousin marriages were reported in 191 families (79.3%), while 31 patients (12.9%) were born to second cousins. The parents of 5 patients (2%) were related as double first cousins, and 2 patients (1%) were born to first cousins once removed. The average coefficient of inbreeding (F) in our study was 0.081. Seventeen patients (6%) had associated comorbid conditions other than IEM. Our study highlights the clinical burden of IEM in Oman and emphasizes the high consanguinity rates among the parents of affected patients.

Clinical and molecular analysis of isovaleric acidemia patients in the United Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD gene.

Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD). Accumulation of isovaleryl-CoA derivatives to toxic levels results in clinical symptoms of the disease. Here, we investigate the clinical and molecular features of Arab patients with IVA. Patients from five unrelated families were evaluated clinically and for defects in the IVD gene. Four novel mutations (p.F382fs, p.R392H, p.R395Q and p.E408K) have been identified with p.R395Q occurring in two families. In addition, molecular modeling of the identified missense mutations predicted their damaging effects on the protein and computational analysis of the p.F382fs mutation predicted the disruption of a 3' splicing site resulting in inactive or unstable gene product. Furthermore, we found an unusual case of a 17 years old female homozygous for the p.R392H mutation with no clinical symptoms. Our results illustrate a heterogeneous mutation spectrum and clinical presentation in the relatively small UAE population.

Identification of mutations underlying 20 inborn errors of metabolism in the United Arab Emirates population.

Inborn errors of metabolism (IEM) are frequently encountered by physicians in the United Arab Emirates (UAE). However, the mutations underlying a large number of these disorders have not yet been determined. Therefore, the objective of this study was to identify the mutations underlying a number of IEM disorders among UAE residents from both national and expatriate families. A case series of patients from 34 families attending the metabolic clinic at Tawam Hospital were clinically evaluated, and molecular testing was carried out to determine their causative mutations. The mutation analysis was carried out at molecular genetics diagnostic laboratories. Thirty-eight mutations have been identified as responsible for twenty IEM disorders, including in the metabolism of amino acids, lipids, steroids, metal transport and mitochondrial energy metabolism, and lysosomal storage disorders. Nine of the identified mutations are novel, including two missense mutations, three premature stop codons and four splice site mutations. Mutation analysis of IEM disorders in the UAE population has an important impact on molecular diagnosis and genetic counseling for families affected by these disorders.

Lipids-risk categories in omani type 2 diabetics: impact of the national cholesterol educational program.

OBJECTIVE: To evaluate the impact of the National Cholesterol Educational Program Adult Treatment Panel III (ATP III) and the Framingham Offspring Study on Omani diabetic subjects. METHODS: 221 subjects with type 2 diabetes (86 females and 135 males) and 156 non-diabetic subjects (70 females and 86 males) aged 30-70 years attending Sultan Qaboos University Hospital between 1999-2002 were recruited. Lipid profile, glucose, %HbA(1c), apoproteinA-1 and apoproteinB were measured. Low density lipoprotein was calculated using the Friedwald formula. ATP-III and Framingham Offspring Study guidelines were used to classify lipid parameters into coronary heart disease-risk categories. RESULTS: Diabetic compared to non-diabetic subjects had significantly higher triglycerides of >1.7 mmol/L (p=0.01) and lower low density lipoprotein cholesterol of >4.2 mmol/L (p=0.012) and, in female subjects only, lower high density lipoprotein cholesterol of <1.15 mmo/L for (p<0.0001). In addition, 57% of diabetic subjects had abnormal aplipoproteinB of >1.2 g/L compared to 49% of non-diabetic subjects. Combined raised levels of triglycerides, apolipoproteinB and low levels of high density lipoprotein were found in 42% of diabetic compared to 26% of the non-diabetic subjects (p=0.05). Diabetic subjects had significantly higher (p=0.008) NCEP risk-score for coronary artery disease, however, only 34% conformed to a NCEP 10-year-risk score of >10%. CONCLUSION: A substantial proportion of the Omani diabetic subjects were dyslipidaemic according to the ATP III guidelines. This study recommends the implementation of a lower cut-off threshold for starting lipid-modifying agents for Omani diabetics when using the 10-year Framingham Risk Scoring equation.

Interleukin-1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population.

BACKGROUND: Gastric cancer (GC) is the most common malignancy in Oman. Interleukin-1beta gene (IL-1B) and interleukin-1 receptor antagonist gene (IL-1RN) polymorphisms have been associated with increased GC risk. No previous studies have examined their role in an Arab population. We tested the associations between polymorphisms of IL1B at positions -31, -511, and +3954 and the IL-1RN polymorphism [variable number of tandem repeats (VNTR) and TC polymorphism at the -2018 position] and GC in Omani Arab patients. METHODS: Genomic DNA was extracted from peripheral blood of 245 control subjects and 118 gastric cancer patients. The DNA samples were analyzed using the TaqMan allelic discrimination test for IL-1B -31, -511, and +3954 polymorphisms and IL-1RN -2018 polymorphism. The VNTR of IL-1RN was genotyped using the polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: There was an association between the presence of IL-1RN*2 allele and gastric cancer [odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.0-3.3, P = 0.04). The GC risk further increased to OR = 3.5 (95% CI = 1.0-11.9) in Helicobacter pylori-positive patients. No association was found between any of the other polymorphisms studied and GC. CONCLUSION: IL-1RN polymorphism increased the risk of GC in an Omani Arab population, consistent with previous reports. In contrast, the IL-1B -31 polymorphism was not associated with an increased GC risk. These findings underscore the role of cytokine gene polymorphisms in the development of GC and further support the ethnic differences in the effect of IL-1B polymorphism on GC carcinogenesis.

A potential role of apolipoprotein B in the risk stratification of diabetic patients with dyslipidaemia.

Diabetic dyslipidaemia is characterised by retention of atherogenic particles, which are depleted of cholesterol. Therefore, calculating or measuring LDL or VLDL cholesterol may not reflect the actual number of these atherogenic particles. We examined the potential role of apolipoprotein B in the risk stratification of Omani patients with type 2 diabetes and dyslipidaemia. Two hundred and twenty-one subjects with type 2 diabetes and 67 healthy controls were recruited. Diabetic subjects had significantly higher serum levels of triglycerides (P<0.0001), non-HDL cholesterol (P<0.0001), and total/HDL cholesterol ratio (P<0.04) and lower levels of HDL cholesterol (P<0.0001) and lipoprotein(a) compared to nondiabetic subjects. The ratio of apoB/LDL cholesterol ratio was significantly higher (P<0.002) among diabetic compared to nondiabetic subjects. Sixty percent of the diabetic subjects with abnormal apoB of >1.2g/L had an LDL cholesterol of less than 4.2 mmol/L compared to 7% of the nondiabetic subjects (sensitivity; 40% versus 93%, respectively). Furthermore, diabetic subjects with ischaemic heart disease (IHD) had significantly higher (P<0.003) apoB/non-HDL cholesterol ratio compared to those without IHD. These findings suggest that the ratios of apoB/LDL cholesterol and apoB/non-HDL cholesterol may have a role in the risk stratification of diabetic patients with dyslipidaemia.