Genetic polymorphisms in the Kuwaiti Arabs

Blood samples were collected from 162 Kuwaiti Arabs. These samples were typed for the ABO, MNSs, Rh, Kell and Duffy blood group systems, serum protein haptoglobins, the red cell isoenzymes acid phosphatase, phosphoglucomutase (locus 1), adenylate kinase, 6-phosphogluconate dehydrogenase, and the lactate and malate dehydrogenase variants. Comparisons were made with serological findings for other Arab populations in the Arabian peninsula.     

Genetic polymorphisms in southwest Alaskan Eskimos.

Allele frequencies of 28 genetic loci were determined in subsets (n ranged from 52 to 698) of a sample of Yupik-speaking Eskimos from southwestern Alaska. Five loci were monomorphic (Kell Kp (b+), ADA1, AK1, HBA, and PGDA). At the other loci, the most frequent alleles were AB00 (0.580), Fya (0.960), Jkb (0.513), Ms (0.333), CDe (0.591), ACPA (0.566), ESD1 (0.890), GLO2 (0.736), GPT1 (0.653), Hp2 (0.654), PGM1 (0.836), PGP1 (0.972), and UMPK1 (0.873). The most frequent immunoglobulin allotype Gm(1;21) occurred with a frequency of 0.829. The HLA alleles that occurred with highest frequencies were A24 (0.626), Bw48 (0.184), Cw3 (0.404), and DR4 (0.329). The average heterozygosity at all loci was 0.423. Based on the presence of the European allotype, Gm3;23;5,11,13, the proportion of European admixture in the Eskimo population was estimated to be 2.1%.     

Genetic polymorphisms in patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.     

Genetic polymorphisms of the endocannabinoid system

Disturbances in the endocannabinoid system has been linked to diseases and conditions such as Parkinson's, schizophrenia, pain, energy metabolism, immune modulation, and bone density. Since the early 1990s, a number of genetic polymorphisms in the genes and proteins of the endocannabinoid system have been characterized. Currently identified genetic polymorphisms of the endocannabinoid system are reviewed here with particular consideration given to polymorphisms linked to drug and alcohol abuse, schizophrenia, other mental disorders, and energy metabolism.     

Genetic polymorphisms in autochthonous Basques from northern Navarre

This survey reports primary results of classical allele frequencies on ten protein loci in a Basque population sample from northern Navarre, the less known from an anthropological and genetic point of view than the populations of the other Basque territories of Spain. Since ancient times this has been a zone of Basque population settlement, and the Basque language (Euskera) still remains deeply rooted among its autochthonous population. A total of 122 blood samples from unrelated northern Navarrese with autochthonous ascendants to the third generation were typed for GC, HP, PI, TF, ACP1, AK1, CA2, ESD, PGD and PGM1 genetic systems. Basque surnames and birthplaces were the criteria used to define family origins. Genetic structure was analyzed on different population hierarchical levels. Northern Navarre seems to be the most genetically deviated area in comparison with other Basque groups. The highest level of differentiation is observed between Navarrese and Alava Basques whereas Guipúzcoa province, the territory adjacent to northern Navarre, presents the lowest genetic distance from the study area. Northern Navarrese show some distinguishing genetic characteristics in relation to other Basque relative samples, which include high frequencies for PI*M1 and TF*C1 and low levels of PGD*C and PGM1*2 alleles. When the genetic data reported here are analyzed jointly with GM allotypes frequencies, the results significantly reinforce the relative position of Navarrese Basques as well as the topology of the Basque cluster on genetic maps. The analysis of relationships among the genetic structures of Basque population samples leads us to ask ourselves which of them fits in best with the ancient Basque population. Classical geographers placed the tribe of the Vascones in the geographical region currently known as Navarre, so extant Navarrese Basques might be considered firm candidates to denote the anthropological and genomic distinctiveness of the ancient Basques.     

Genetic polymorphisms of HSP70 in age-related cataract

Polymorphisms have been identified in several HSP70 genes, which may affect HSP70 repair efficiency. We investigated the association of the polymorphisms in HSPA1A, HSPA1B, and HSPA1L genes in the HSPs repair pathway with the risk of cataract in a Chinese population. The study included 415 cataract patients and 386 controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism method. HSPA1B 1267 A/A genotype seems to have a protective role against cataract (p = 0.014, odds ratio (OR) = 0.664, 95 % confidence intervals (CI) = 0.480–0.919), and the G allele (p = 0.057, OR = 1.216, 95 % CI = 0.999–1.479) does not seem to have a deleterious role in the development of cataract. Haplotypes with frequencies of GAT were significantly different than those of controls (p = 0.005). In HSPA1A G190C and HSPA1L T2437C polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared to controls. We conclude that the A/A genotype of HSPA1B A1267G polymorphism seem to have a protective role against age-related cataract.     

Genetic polymorphisms in isolated Sherpa populations of Nepal

Data are reported on the incidence of variants in the ABO blood group system, four red cell enzyme polymorphisms, and the PTU taster/non-taster polymorphism in 155 Sherpas and Tamangs living in two villages in the isolated Rolwaling valley in east Nepal. The incidence of phenotype AB was unexpectedly high in one village, as has been reproted insome other high-altitude populations: possible causes are discussed. Each of the other polymorphisms has a different pattern of distribution between the populations studied; the Sherpas' allele distribution in the phosphoglucomutase (PGM) system seems to be distinct from the surrounding populations'. ABO gene frequencies suggest affinities between Sherpas in the study villages and old- and new-clan Sherpa populations, respectively, in Solu and Khumbu.     

Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population

OBJECTIVE: The aims of the present study were to assess whether the glutathione S-transferase T1 (GSTT1), M1 (GSTM1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) genotypes are associated with type 2 diabetes mellitus (T2 DM) and to ascertain whether the levels of blood lipids given exposure to diabetes are modified by the specific genetic polymorphisms of GSTT1, GSTM1, and NQO1. METHODS: This case-control study was conducted on 200 subjects. The genotypes were determined using a polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. RESULTS: The GSTT1-present genotype conferred a statistically significant 0.49-fold reduction in risk of T2 DM relative to the null genotype. Individuals with GSTT1-null or GSTM1-null genotype had higher levels of low-density-lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a), respectively. There was no association between either GSTM1 or NQO1 polymorphism and risk of T2 DM. CONCLUSION: The present results suggest that the GSTT1 gene may contribute to the development of T2 DM and may be one of the candidate genes of T2 DM in Chinese population.     

Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus

Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.     

Genetic polymorphisms in lung disease: bandwagon or breakthrough?

The study of genetic polymorphisms has touched every aspect of pulmonary and critical care medicine. We review recent progress made using genetic polymorphisms to define pathophysiology, to identify persons at risk for pulmonary disease and to predict treatment response. Several pitfalls are commonly encountered in studying genetic polymorphisms, and this article points out criteria that should be applied to design high-quality genetic polymorphism studies.     

Genetic polymorphisms for vascular endothelial growth factor in perinatal complications

Low birth weight (LBW) infants have increased susceptibility to perinatal complications. An immature and impaired vascular system may possibly participate in these complications. There is evidence that supports the notion that vascular endothelial growth factor (VEGF), which is an essential regulator of embryonic angiogenesis, plays a central role in the pathogenesis of perinatal complications. We aimed to test whether functional genetic polymorphisms of VEGF are associated with the risk of preterm birth or perinatal morbidity. We enrolled 128 LBW infants (< or = 1500 grams). VEGF T-460C, VEGF C-2578A and VEGF G+405C polymorphisms were determined by real-time PCR or PCR-RFLP, respectively. Their genotypes were compared with VEGF genotypes of 200 healthy, term neonates. The prevalence of the VEGF+405 C allele was higher in LBW infants than in healthy, term neonates (OR [95% CI]: 1.29 [1.01-1.65]). Carrier state for the VEGF -2578A allele was an independent risk factor for enterocolitis necrotisans (NEC) (adjusted OR [95% CI]: 2.77 [1.00-7.65]). The carrier state for the VEGF -2578AA genotype was associated with a decreased risk of acute renal failure (ARF) (adjusted OR [95% CI]: 0.2 [0.05-0.78]). These results suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C-2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF.     

Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus

Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110+/-68 nmol/ml/min) and T2DM patients (118+/-69 nmol/ml/min) compared to the control persons (203+/-58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes.     

Genetic diversity in tetraploid switchgrass revealed by AFLP marker polymorphisms

Switchgrass (Panicum virgatum) is a perennial warm-season grass native to North America that has been identified as a dedicated cellulosic biofuel crop. We quantified genetic diversity in tetraploid switchgrass germplasm collected at Oklahoma State University and characterized genetic relatedness among the collections from distinct regions. Fifty-six tetraploid accessions, including seven upland and 49 lowland genotypes from throughout the US, were examined. The amplified fragment length polymorphism (AFLP) procedure was utilized to generate DNA profiling patterns that were scored visually. Sixteen selective AFLP primer combinations were used to amplify 452 polymorphic bands. The accessions' genetic similarity coefficients, UPGMA (unweighted pair-group method with arithmetic averaging) cluster analysis and principle coordinate analysis, were performed. The upland and lowland accessions clustered according to ecotypes, with one exception (TN104). Genetic similarity coefficients among the accessions ranged from 0.73 to 0.95. Analysis of molecular variance (AMOVA) was performed, showing significant differences between the upland and lowland genotypes. The trnL marker confirmed that TN104 was a lowland genotype, but the trnL marker identification of upland and lowland genotypes was not consistent with the AFLP analysis in two germplasms (Miami and AR4).