Relevance of KISS1 gene polymorphisms in susceptibility to polycystic ovary syndrome and its associated endocrine and metabolic disturbances.

Background: Variations in KISS1 may be an emerging factor in polycystic ovary syndrome (PCOS) We hypothesised links between KISS1 polymorphisms in PCOS and its associated endocrine and metabolic disturbances. Methods: The study included 104 PCOS women and 109 controls. Endocrine (kisspeptin, LH, FSH, LH-FSH ratio, oestradiol) and metabolic (cholesterol, triglycerides, HDL, LDL, insulin and glucose) parameters were measured. PCR and nucleotide sequencing were carried out to screen single nucleotide polymorphisms (SNPs) of KISS1. Endocrine and metabolic parameters of PCOS women were compared in the genotypes. Results: Three novel SNPs (rs1213704663C>G, rs1481572212T>G and rs775770652G>A) were detected in KISS1. Of these SNPs, the genotype and allele frequencies of rs1213704663C>G were all significantly associated p<0.001 with PCOS. The LH and oestradiol hypersecretion, and increased LH-FSH ratio of PCOS women were significantly influenced by the GG genotype of rs1213704663, but, this SNP did not influence kisspeptin levels. The other two SNPs rs1481572212T>G and rs775770652G>A exhibited no clinical significance. Conclusion: rs1213704663C>G variation in KISS1 is linked to PCOS and its associated endocrine and metabolic disturbances (LH and oestradiol hypersecretion, and increased LH/FSH).

Leptin concentration during different stages of pregnancy.

OBJECTIVES: To determine the levels of leptin in pregnant females during different stages of pregnancy and to correlate these levels to maternal weight, body mass index (BMI), neonate weight and neonate BMI. MATERIAL & METHODS: A case control study was carried out in which 60 pregnant females were enrolled, but only 36 completed the study and 30 non-pregnant females were used as controls. Blood samples were collected at the 1st trimester, 2nd trimester and 3rd trimester, and after delivery. Serum was used for the estimation of leptin (by radioimmunoassay). RESULTS: The results showed that the levels of leptin were significantly higher in pregnant females compared to non-pregnant females, but significantly decreased after delivery. In pregnant females with gestational diabetes the leptin level was insignificantly higher. CONCLUSION: The increase of leptin levels may be due to the stimulatory effect of insulin on leptin secretion from adipose tissue.

Overweight and obesity in Saudi females of childbearing age.

OBJECTIVE: Overweight and obesity are among the most frequently encountered multifactorial disorders in most populations of the world. The aim of this study was to determine the prevalence of overweight and obesity in Saudi females of childbearing age. MATERIALS AND METHODS: The study was approved by the University Scientific Committee. It included a group of 600 randomly recruited healthy females with age ranging from 16-45 y. Four hundred and twenty one were students and 179 were housewives attending outpatient clinics for minor illnesses. Informed consent was obtained. Height and weight were recorded on one occasion. Body mass index (BMI) was calculated. RESULTS: Height, weight and BMI showed normal Gaussian distribution in these females and there was a significant positive correlation between BMI and age of each subject (r=0.505; P

A comparative study of haematological parameters in children suffering from sickle cell anaemia (SCA) from different regions of Saudi Arabia.

Sickle cell anaemia (SCA) occurs frequently in several regions of Saudi Arabia but the haematological and clinical presentations are significantly variable. We investigated 264 Saudi children suffering from SCA originating from different regions of Saudi Arabia. Normal children from the same region were used as controls. Freshly obtained blood samples from patients and controls were used to estimate haematological parameters, red cell indices, Hb A2 and Hb F levels. The results of children from the different regions were separately analysed using the Statistical Analysis System (SAS). Significant variations were seen in the haematological parameters in SCA patients compared to controls in each region. In addition, comparison of patients from different areas also showed wide variations. The highest levels of haemoglobin, red blood cells and haematocrit were in the SCA children from the eastern province, and the lowest levels were from those in the western province. Red cell indices and Hb A2 levels did not differ significantly but HbF levels were significantly higher compared to the control group. Inter-regional differences were seen in the Hb F level. A slight but statistically significant increase was seen in the total haemoglobin with Hb F. This paper compares the haematological parameters of SCA in different regions of Saudi Arabia and shows a significant haematological heterogeneity in SCA in Saudis.

Evaluation of serum cholesterol and triglyceride levels in 1-6-year-old Saudi children.

Estimations of cholesterol and triglyceride in serum are frequently requested tests due to the close association between elevated levels of these parameters and the risk of arteriosclerosis later leading to cardiovascular disease. Since lipid levels in children show considerable variations in different populations, this study was conducted with the aim of investigating levels of cholesterol and triglycerides in Saudi children less than 6 years old. The study group comprised 582 children with ages ranging from 1 to 6 years, randomly selected during a household screening programme. Fasting blood was used for the estimation of cholesterol and triglyceride using an autoanalyser. The overall range for cholesterol was 2.1-5.7 mmol/l and for triglyceride it was 0.1-1.84 mmol/l. The children were separated into five further groups depending on age, and the levels of cholesterol and triglycerides were obtained in each age group. Using published guidelines for cholesterol and triglyceride levels, to estimate 'borderline' and 'high risk' for arteriosclerosis and coronary artery disease, the prevalence of both risk groups were calculated in Saudi children. A total of 6.87 per cent of children fell in the borderline risk and 1.55 per cent in the high-risk group using cholesterol levels, while 1.89 per cent fell in the borderline-risk group and 1.2 per cent in the high-risk group using triglyceride levels. This paper presents the lipid values and discusses the need for lipid awareness programmes in the country.

Prevalence of hypertension in obese and non-obese Saudis.

OBJECTIVE: Obesity occurs at a high prevalence in the Saudi population. Studies in literature show that hypertension occurs more frequently in obese individuals. This study was designed to determine the prevalence of hypertension in obese Saudis in comparison with results obtained in non-obese individuals. METHODS: The screening involved a statistically designed household screening program. Only adults 14-70 years of age were included in the study. Blood pressure (systolic and diastolic) was measured when the individuals were in sitting position and height and weight were used to calculate Body Mass Index. All individuals with Body Mass Index > 30 were classified as obese and hypertension was measured as systolic blood pressure > 140 and diastolic blood pressure > 90 or both. The prevalence of hypertension was calculated in the obese and non-obese group. Chi square analysis was carried out to determine the significance of the difference in prevalence in different groups. RESULTS: In the non-obese males and females the prevalence of hypertension was 4.8% and 2.8%. While in the obese group the prevalence was almost 1.6 times higher in the males (8%) and 3.52 times higher (8%) in the female obese. The results were separated on the basis of the province to which the population belonged and hypertension prevalence was calculated in the obese and non-obese. In each region the prevalence of hypertension was higher in the obese group compared to the non-obese group. Non-obese females had significantly lower hypertension prevalence than the male in the same province but the hypertension prevalence was higher in the females compared to the male in the obese group. Male in the Eastern, Southern and Western provinces did not show an increased hypertension prevalence in the obese. CONCLUSION: Since the prevalence of obesity is high in Saudis and since obesity and hypertension occur together and cause serious complications, it is strongly suggested that measures are adopted to decrease prevalence of obesity and its underlying complications. Awareness programs are required at the level of the general public for successful implication of preventive programs.

Normal reference values for hematological parameters, red cell indices, HB A2 and HB F from early childhood through adolescence in Saudis.

BACKGROUND: Values of hematological parameters are affected by factors such as age, sex, ethnic background and social, nutritional and environmental factors. The objective of this study was to determine the values of hematological parameters, red cell indices and Hb A2 and Hb F levels in normal Saudi children, living in the Central Province of Saudi Arabia. MATERIALS AND METHODS: The study was carried out on 1526 apparently healthy children, with ages ranging from 1-15 years, and selected during a household screening program. Hematological parameters, red cell indices, and hemoglobin types (Hb A2 and Hb F) were estimated, and the children were divided into 15 groups depending on the age. Male and female children were separated, and the mean and standard deviation of each parameter was calculated for each age group. RESULTS: No significant differences were observed in the red cell count in the male and female children. White blood cells gradually decreased from 2 years onwards, while hemoglobin and hematocrit levels increased significantly from 2 to 15 years. Mean cell volume and mean cell hemoglobin also showed slight increases, while mean cell hemoglobin concentration remained more or less constant. Hemoglobin A2 and Hb F showed slight but nonsignificant fluctuations. Comparison of the results with those reported in the literature shows that Saudi children have some values similar to Caucasians, while others have values which are intermediate between Caucasians and African children. CONCLUSION: The values reported in this study can be used as normal reference values for Saudi children and adolescents.

G6PD deficiency, distribution and variants in Saudi Arabia: an overview.

BACKGROUND: The first report of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Saudi population of the Eastern Province paved the way for extensive investigations to determine the distribution and molecular pathogenesis of G6PD deficiency in Saudis in different parts of the country. MATERIALS AND METHODS: During a national study lasting from 1982 to 1993, 24,407 Saudis in 31 different areas of Saudi Arabia were screened for G6PD deficiency using spectrophoretic estimation of the enzyme activity and electrophoretic separation of the phenotypes. RESULTS: The results in the males and females were separately analyzed, and showed a statistically significant difference in the frequency in the male (0.0905) and female (0.041) population (P<0.05). The frequency in the male varied from 0 to 0.398, and in the female from 0 to 0.214. The phenotypes identified included G6PD-A(+), G6PDA-Mediterranean and G6PD-A(-), and G6PD-Med-like with G6PD-B(+) as the normal phenotype in all areas. CONCLUSION: This study shows that G6PD deficiency is a frequently identified single-gene disorder in Saudi Arabia and G6PDA-Mediterranean is the major variant producing the severe deficiency state in this population.

Association of hypertension and non-insulin-dependent diabetes mellitus in the Saudi population.

BACKGROUND: Saudi Arabia has a high prevalence of diabetes mellitus (DM). Several studies have shown that hypertension (HT) occurs frequently in obese individuals. This study was conducted to determine the prevalence of HT in Saudi diabetic patients. SUBJECTS AND METHODS: A total of 13,519 nondiabetic and 1286 diabetic adult subjects diagnosed during the National Program for the Study of DM, in which household screening was carried out, were included in the study. The diagnosis of DM and HT was based on the criteria of the World Health Organization. RESULTS: From the total group, the prevalence of HT in nondiabetic males and females was 4.48% and 2.8%, respectively, while it was 11.44% and 15.98% in the diabetic males and females, respectively. The subjects were classified according to the province to which they belonged, and the prevalence of HT was calculated in the diabetic and nondiabetic group. In the Central, Eastern and Western Provinces, female diabetics had a significantly higher HT prevalence compared to male diabetics, however, in the Southern and Northern Provinces, the prevalence rate was almost the same. In all provinces the increase in prevalence of HT in diabetics was significantly higher in the females compared to the males. CONCLUSION: Since HT prevalence increases significantly in diabetics, and this association leads to several cardiovascular complications, it is necessary to adopt measures for the control of DM and HT in the Saudi population.

Prevalence of plasma lipid abnormalities in Saudi children.

BACKGROUND: Lipid levels in children vary in different populations. Due to a close association between high lipid levels and development of atherosclerosis, considerable interest has been directed to investigating lipid levels in children. MATERIALS AND METHODS: We conducted this study on 2914 children with ages ranging from 1 year to <15 years, randomly selected during a national household screening program. Fasting blood samples were used for estimation of triglyceride and cholesterol levels. RESULTS: The overall range for cholesterol was 2.0-5.7 mmol/L and for triglyceride the overall range was 0.1-1.7 mmol/L. The children were separated into 14 groups depending on age, and the cholesterol and triglyceride levels were calculated in each age group. Using published guidelines for estimating "borderline" and "high risk" for coronary artery disease from cholesterol and triglyceride levels, the prevalence of borderline and high-risk groups was calculated. 7.72% of the children fell in the borderline risk group and 1.55% in the high-risk group using cholesterol values, while using triglyceride values, 1.4% and 0.55% fell in the borderline and high-risk groups, respectively. The prevalence of abnormality varied in the different age groups. CONCLUSION: The paper discusses the need for a lipid awareness program in Saudi children in an attempt to decrease the complications associated with dyslipidemias during adulthood.

Xmn I polymorphic site in Yemeni sickle cell disease patients.

To investigate the molecular basis of severe clinical presentation in sickle cell disease (SCD) patients in Yemen, this study was conducted on 30 Yemeni SCD patients living in Riyadh and attending King Khalid University Hospital. Seven individuals without SCD were used as controls. Haematological parameters, red cell indices, Hb A2 and Hb F levels were estimated and haemoglobin variant were identified on electrophoresis profiling. DNA was extracted from the buffy coat separated from fresh blood samples and was treated with the restriction endonuclease: Xmn I. The fragments generated were separated on electrophoresis, transferred to nitrocellulose and hybridized to a 32P-labelled probe of gamma-globin gene. After extensive washing, two bands, 8.1 kb and 7.0 kb in size, were obtained. The frequency of occurrence of the presence of Xmn I polymorphic site (7.0 kb fragment) and its absence (8.1 kb fragment) were documented. The results in Yemeni SCD patients were compared with the results obtained previously in Saudi Arabs. Of the 30 SCD patients from Yemen 29 had only the 8.1 kb fragment and one had only the 7.0 kb fragment. This gave the frequency of 0.966 for the absence (-) and 0.033 (+) for the presence of Xmn I polymorphic site. This is the same result as that reported earlier for SCD patient from southwestern Saudi Arabia [(-) = 0.966; (+) = 0.033] but is significantly different from that reported in the eastern province [(-) = 0.068; (+) 0.932)] of Saudi Arabia. This paper presents the nature of molecular linkage in SCD patients from Yemen.

Prevalence of overweight and obesity in diabetic and non-diabetic Saudis.

A total of 14,660 individuals were included in the study. A fasting blood sample and 2-hour post-glucose load blood sample from each participant were analysed for blood sugar. Participants were classified as diabetic or non-diabetic and as either obese (BMI > 30 kg/m2), overweight (BMI 25-29.9 kg/m2) or normal (BMI < 25 kg/m2). The prevalence of obesity was calculated in the total sample and separately for diabetic and non-diabetic males and females. The results showed obesity and overweight in 13.05% and 27.23% of males and 20.26% and 25.20% of females respectively. The prevalence of both obesity and overweight were significantly higher among diabetics than non-diabetics. In each province, diabetics had a significantly higher prevalence of obesity than non-diabetics. Several interprovincial variations were seen. Public education on obesity and overweight and ways to decrease them are recommended in Saudi Arabia.

Prevalence of overwieght and obesity in diabetic and non-diabetic Saudis

A total of 14 660 individuals were included in the study. A fasting blood sample and 2-hour post-glucose load blood sample from each participant were analysed for blood sugar. Participants were classified as diabetic or non-diabetic and as either obese [BMI > 30 kg/m2], overweight [BMI 25-29.9 kg/m2] or normal [BMI < 25 kg/m2]. The prevalence of obesity was calculated in the total sample and separately for diabetic and non-diabetic males and females. The results showed obesity and overweight in 13.05% and 27.23% of males and 20.26% and 25.20% of females respectively. The prevalence of both obesity and overweight were significantly higher among diabetics than non-diabetics. In each province, diabetics had a significantly higher prevalence of obesity than non-diabetics. Several interprovincial variations were seen. Public education on obesity and overweight and ways to decrease them are recommended in Saudi Arabia

The pattern for common anaemia among Saudi children.

Anaemia is of frequent occurrence in children in different parts of the world and poses a significant health problem. A few isolated reports indicate that anaemia occurs at a high prevalence rate in Saudi Arabia though the actual prevalence in several regions is not known. The aim of the present study was to determine the prevalence of different types of anaemias in Saudi children in different areas of the country. Blood samples were collected from 5381 children less than 14 years of age, and haematological analysis and red cell indices were determined. The results of haematological parameters were used to group the children as anaemic (Hb < 11.2 g/dl) and non-anaemic (Hb > 11.2 g/dl) and the red cell indices were used to classify the anaemia as hypochromic-microcytic, normochromic-normocytic, and normochromic-macrocytic. The overall prevalence of anaemia in Saudi children was 24.8 per cent. The prevalence was highest in the children from the Eastern province (41.3 per cent) and lowest in the central province (16.5 per cent). Within each province differences were obvious in the prevalence of anaemias in the different areas. The majority of the anaemia in the eastern and south-western provinces was hypochromic-microcytic, while in the north-western and central provinces normochromic-normocytic anaemia occurred most frequently. Macrocytic anaemia was not encountered in any of the screened areas of the central province and many areas of the eastern province. However, in north-western and south-western provinces it occurred at a frequency of 0.15-3.4 per cent. The data show that anaemia is a frequent problem in Saudi children living in different parts of Saudi Arabia and emphasizes the need for nutritional and genetic assessment to determine the nutritional contributions to anaemias and hence the correction of nutritional anaemias by proper dietary intervention.

Nitric oxide production is enhanced in patients with heat stroke.

OBJECTIVE: To determine whether nitric oxide (NO) production is increased in heat stroke (HS) patients. DESIGN: A prospective analysis of nitrite and nitrate (NO2*/NO3) levels in ten HS patients was performed at the HS center in Makkah, Saudi Arabia. METHODS: Plasma (NO2*/NO3) levels were determined spectrophotometrically before cooling (0 time), and at 6, 12, and 24 h post-cooling. RESULTS: The mean level of NO in the ten HS victims before cooling was significantly higher than in eight control patients (35.6+/-37.0 vs. 3.0+/-4.2 micromol/l; p<0.01). The levels were higher in non-survivors than in survivors. NO also correlated positively with the Acute Physiology and Chronic Health Evaluation II score (r = 0.72, p<0.018). There was no correlation between the NO level before cooling and blood pressure, rectal temperature, or cooling time. CONCLUSION: HS is associated with excessive NO production, the magnitude of which is proportional to the severity of illness. NO may be an important mediator and integral part of the pathophysiological processes resulting in HS and may be a central factor linking the neurological and cardiovascular abnormalities observed in HS.

Alpha thalassaemia in Yemeni children with sickle cell disease.

Alpha thalassaemia frequently occurs in several of the Middle Eastern populations. This study was conducted on 26 sickle cell disease (SCD) patients from Yemen and 19 normal children (Hb AA) living in Riyadh, Saudi Arabia. Blood samples were extracted by venepuncture, and haematological and biochemical parameters were estimated. DNA was extracted from the buffy coat and analysed for alpha-gene arrangement using Bam HI and Bgl II. The frequency of alpha-gene deletion in the total Yemeni group (26 SCD + 19 Hb AA) was 0.311 for one alpha-gene deletion (-alpha/alpha alpha) and 0.13 for two alpha-gene deletions (-alpha/-alpha). When separated on the basis of the Hb phenotype the alpha-gene deletion frequency was significantly higher (-alpha/alpha alpha = 0.346 and -alpha/-alpha = 0.231) in the SCD patients compared to the normal Hb AA group (-alpha/alpha alpha = 0.263 and -alpha/-alpha = 0). In the Hb AA group one child had triple alpha-gene arrangement (alpha alpha alpha/alpha alpha) giving an overall frequency of triple alpha-gene as 0.022. Haematological parameters showed variations in the SCD patients with and without alpha-gene deletion. This paper shows for the first time that alpha-gene deletion occurs in the Yemenis and the frequency is higher in patients with SCD. Further population-based studies are required to determine the exact frequency of the different types of alpha-thalassaemias in the overall Yemeni population.

Appraisal of sickle-cell and thalassaemia genes in Saudi Arabia.

A comprehensive national survey of the distribution of the sickle-cell (Hb S) gene and thalassaemia genes was initiated in 1982, with more than 30,055 blood samples collected. The Hb S, alpha- and beta-thalassaemia gene frequency range was 0.005-0.145, 0.01-0.40 and 0.01-0.15 respectively in various areas of Saudi Arabia. We present here an appraisal of sickle-cell and thalassaemia gene occurrence in the Saudi population, based on our studies conducted over 10 years in different regions of Saudi Arabia.

Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease.

We collaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the origin of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula.

Pattern for alpha-thalassaemia in Yemeni sickle-cell-disease patients.

A group of Yemeni patients with sickle-cell disease (SCD) and normal Hb AA individuals living in Riyadh were studied to determine the incidence of the alpha-gene molecular defect. Blood samples were obtained from 26 SCD patients and 19 controls (the Hb AA group). In the SCD patients the frequency of single alpha-gene deletion (-alpha/alpha alpha) was 0.346, compared to 0.263 in the Hb AA group. The frequency of two gene deletion (-alpha/-alpha) was 0.231 (0.0 for the Hb AA group). In one Hb AA case, a triple alpha-gene arrangement (alpha alpha alpha/alpha alpha) was found (frequency 0.053). The results suggest that alpha-thalassaemia occurs frequently in Yemeni SCD patients. Further studies to determine the overall frequency of alpha-thalassaemia in the Republic of Yemen would be of value for patient management.

Molecular studies on Yemeni sickle-cell-disease patients: Xmn I polymorphism.

Our studies of the Saudi population have shown that in patients with mild presentation of sickle-cell disease (SCD) from Saudi Arabia's eastern region, the prevalence of polymorphic sites is high. However, the prevalence is very low in patients with severe SCD from the south-west of the country. We expanded these studies to a group of Yemeni patients with severe SCD, resident in Riyadh. We investigated a total of 60 chromosomes carrying the sickle-cell (Hb S) gene and 14 chromosomes carrying the Hb A gene. Amongst the Hb AA group, the prevalence was 42.9% and 57.1% for the presence (+) and absence (-) of Xmn I polymorphic sites. In the Hb SS individuals, the prevalence of Xmn I polymorphic sites was similar to the prevalence reported in the south-western region of Saudi Arabia.