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).

Thermal regulatory dysfunction of growth hormone in classical heat stroke.

Growth hormone (GH) secretion associated with classical (non-exertional) heat stroke (HS) was evaluated in 26 HS victims and 10 control (non heat-exhausted) subjects during the annual Hajj in Makkah, Saudi Arabia. On admission to the HS treatment unit, the GH level was 1.54 +/- 0.14 ng/ml (approximately 3.5-fold higher in the HS victims compared to controls; p = 0.005). The GH levels subsequently declined by 78% by 24 h. The categorized GH response was significantly associated with survival for those subjects with a GH level of < 5.53 ng/ml by 6 h (chi-squared test; p = 0.06). In those patients who died (N = 6), there was a continued increase in GH levels from the time of admission, which peaked at 6 h. In those patients who survived, the GH levels peaked at the time of admission and declined rapidly thereafter. There was a direct correlation of age and GH level upon admission (p = 0.02), as well as to peak GH (p = 0.041). However, there was no relationship of GH level to either body core temperature or the cooling time. In summary, HS induced significant GH secretion. The degree of GH response was not related to the body core temperature and was more pronounced in older individuals and in those that died. Although patients with GH deficiency and HS are characterized by anhidrosis/hypohidrosis, there does not appear to be dysfunction of GH response to heat stress-associated HS. In contrast, a vigorous GH response at 6 h suggested a worse outcome.

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 1-antitrypsin serum levels in widespread bronchiectasis.

This study found significantly higher serum levels of alpha 1-antitrypsin (alpha 1-AT) in 35 patients with widespread bronchiectasis compared with healthy controls. The results are in contradiction with a previous study and four case reports which found an association between alpha 1-AT deficiency and bronchiectasis. However, the validity of the association has been questioned in the literature on the grounds that most of the patients in those reports had other possible aetiologies for their bronchiectasis. We believe the raised level of alpha 1-AT in our patients represents a non-specific acute phase response to bronchial infection. Further studies are needed to clarify whether bronchiectasis, like emphysema, can be a manifestation of alpha 1-AT deficiency.

Establishment of a normal reference range for alpha 1-antitrypsin in Saudis using rate nephelometry.

Alpha 1-antitrypsin level was estimated in 543 healthy males and 603 healthy females using rate nephelometry, in order to establish a "normal reference range" in Saudis. A significantly higher mean and range were encountered in the females than in the males, and a positive correlation was obtained between the alpha 1-antitrypsin level and age. Since alpha 1-antitrypsin showed a positively skewed distribution, the normal reference ranges were established using the 2.5th to 97.5th percentile values. This article presents the normal reference range for alpha 1-antitrypsin as 100 to 250 mg/dl in children under 10 years of age, 95 to 275 mg/dl in adult males and 100 to 350 mg/dl in adult females. The results are discussed in light of the significant differences encountered in comparison with the results reported elsewhere and by the manufacturers of the kits.

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.

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.

Obesity and overweight in type II diabetes mellitus patients in Saudi Arabia.

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Relationship between obesity, overweight and plasma lipids in Saudis.

Full text is available as a scanned copy of the original print version.

Obesity and overweight in type II diabetes mellitus patients in Saudi Arabia.

Full text is available as a scanned copy of the original print version.

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.

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.

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.

Glutathione reductase deficiency in Saudi Arabia.

Glutathione reductase (GR) is a ubiquitous enzyme required for the conversion of oxidized glutathione (GSSG) to reduced glutathione (GSH) concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate (NADPH) in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide (FAD) and the activity coefficient (AC) was determined. Samples with low GR activity (> 2.0 IU/g haemoglobin) both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC > or = 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified.

Diabetes mellitus, hypertension and obesity--common multifactorial disorders in Saudis.

Diabetes mellitus, hypertension and obesity are among the multifactorial disorders that occur at a higher prevalence in older age groups. Their prevalence is affected by both genetic and environmental factors. We investigated the distribution of diabetes mellitus, hypertension and obesity in Saudi males and females by conducting a household screening survey during the period 1992-1996 of the adult population (> 14 years) in five different areas of Saudi Arabia. Height, weight, age and other essential details were recorded and diastolic and systolic blood pressures measured. Glucose levels were measured in blood taken after fasting and 2 hours after a glucose load. The data were used to classify the individuals as diabetic, glucose intolerant and normal, using WHO criteria. The individuals were further classified as type 1 diabetes mellitus and type 2 diabetes mellitus. The overall prevalence of diabetes mellitus was 9.7% and 7.0%, obesity 13.05% and 20.26%, overweight 27.23% and 25.20%, and hypertension 5.39% and 3.65% in the adult male and female populations respectively. A significant increase was observed in the prevalence of diabetes, obesity and hypertension with age in both males and females. In addition, the prevalence of obesity and overweight was significantly higher in the individuals with diabetes mellitus.

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.

Glucose 6-Phosphate dehydrogenase deficiency genetic, pathophysiological and therapeutic aspects.

Glucose 6-phosphate dehydrogenase (G6PD) is the first enzyme of the pentose phosphate pathway. It exists in over 250 variants which are divided broadly into five classes on the basis of residual enzyme activity and clinical manifestations. The variants with reduced activity result in G6PD deficiency. This is inherited as an X-linked recessive disorder and occurs at a much higher frequency in the male than in the female. Most G6PD deficient individuals show no clinical abnormality under normal conditions, but acute hemolytic crisis may occur. Several nonhemolytic abnormalities occur as well in G6PD deficients at a higher frequency than in nondeficients. Several nonhemolytic abnormalities occur as well in G6PD deficients at a higher frequency than in nondeficients. The genetic, pathophysiologic, and therapeutic aspects of G6PD deficiency are presented; and the possibility of genetic counselling, care in blood banks, and benefits of education the G6PD deficients are discussed.

The frequency of glucose-6-phosphate dehydrogenase phenotypes and sickle cell genes in Al-Qatif oasis.

This study was conducted on a selected population of Al-Qatif in Eastern Saudi Arabia to determine the gene frequencies of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell (HbS) genes and to study the extent of interaction between the two genes. A total of 960 blood samples collected from Saudi males (515) and females (445) attending the outpatient clinics and hospitals for minor illnesses were subjected to electrophoresis for separation of hemoglobin types and G-6-PD phenotyping and for spectrophotometric determination of G-6-PD activity. The prevalence of HbS heterozygotes was 25.9%, Hb S/b_-thalassemia was 1.563% and HbS homozygotes was 2.917%. The overall gene frequency of HbS was 0.1666. Severe glucose-6-phosphate dehydrogenase deficiency was encountered in a large percentage of the population with a frequency of 0.392 for G-6-PD Mediterranean and 0.0058 for G-6-PD-A- in the male population and 0.2020 and 0.0112 for G-6-PD Mediterranean and G-6-PD-A- in the female population respectively. Partial deficiency was encountered at a frequency of 0.0272 and 0.0697 in the male and female populations respectively. G-6-PD deficiency caused by G-6-PD Mediterranean occurred at a higher frequency in individuals with normal hemoglobin (Hb AA) (0.414 and 0.217 in males and females respectively) compared to the HbS heterozygotes (0.338 and 0.168 in males and females respectively) and HbS homozygotes and HbS bo-thalassemia cases (0.3125 and 0.1852 in males and females respectively). Compared to all areas of Saudi Arabia, Al-Qatif had the highest gene frequencies for HbS and G-6-PD deficiency genes.

The frequency of glucose-6-phosphate dehydrogenase phenotypes and sickle cell gene in Al-Qassim.

This study was conducted in the Al-Qassim area located in the central province of Saudi Arabia in order to estimate the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell genes (Hb S). Blood samples from 1,015 Saudi males and females were analyzed for hemoglobin types, G-6-PD phonotypes and G-6-PD levels. Only two cases heterozygous to Hb S (ie Hb AS) were identified and the frequency of Hb S gene was 0.000985. The normal G-6-PD was G-6-PD-B+ occuring at a frequency of 0.944 and 0.966 in the male and female population, respectively. Variants identified included G-6-PD-A+, G-6-PD-Mediterranean, G-6-PD-A-, and G-6-PD-Mediterranean-like at frequencies of 0.0164, 0.0282, 0.0023, 0.0094 in the males and 0.0068, 0.0085, 0, 0.0102 in the female population, respectively. The severe G-6-PD deficiency was due mainly to G-6-PD Mediterranean and only one male with G-6-PD-A- (0.0023) was identified. These results showed that Al-Qassim had the lowest frequency of Hb S and G-6-PD deficiency genes compared to all other regions of Saudi Arabia that have been screened thus far.