Endothelial nitric oxide synthase (eNOS) VNTR as a probable marker in type 2 diabetes mellitus.

Background: The gene encoding eNOS is located on chromosome 7q36, a genetic region previously linked to metabolic syndrome, cardiovascular and renal diseases. Generally, in diabetes there are numerous genes involved, each being a small contributor in type 2 diabetes mellitus (T2DM) manifestation. A 27 bp variable number of tandem repeat (27 bp VNTR a/b) in intron 4 of enos gene has gained attention and this polymorphism may affect the expresssion of eNOS. We studied the association of eNOS-27 bp VNTR with T2DM in north indian population. Material and methods: Blood samples were collected in 0.5 M EDTA from 200 T2DM patients and 210 age/sex matched healthy controls. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) using the salting out method. The 27-VNTR polymorphism was determined by standard PCR amplification using forward and reverse primers 5'-AGGCCCTATGGTAGTGCCTTT-3’ and 5'-TCTCTTAGTGCTGTGGTCAC-3’ respectively. The genotypes were determined by analyzing the amplified products on 2% agarose gels. Genotypic and allelic frequencies were calculated by SPSS (version 15.0). Results: Clinical and biochemical profiles of healthy controls and T2DM cases as well as gender wise comparisons showed significant association in certain parameters (p<0.001). Five different alleles (I, II, IV, V and VI) were found in the study population. The genotypic frequency was significantly associated with T2DM (P <0.001). Conclusion: A significant role of allele ‘I’ in T2DM susceptibility was an interesting observation. Therefore, The 27 bp VNTR in eNOS gene polymorphism can be used as a probable marker in determining susceptibility to T2DM in north Indian population.

Association Study Between Dopamine Transporter Gene 40 bp VNTR and Antipsychotics-Induced Restless Legs Syndrome / 수면정신생리

OBJECTIVES: The pathophysiology of restless legs syndrome (RLS) is not obvious, but many promising theories involve dopaminergic deficiency and genetic causes. The RLS is presumed to occur more frequently among schizophrenic patients who take antipsychotics, most of which blocks the dopamine receptors. This study aimed to investigate whether dopamine transporter gene (DAT1) 40 base pair (bp) variable number of tandem repeat (VNTR) polymorphism is associated with the antipsychotic-induced RLS in schizophrenia. METHODS: We determined the diagnosis of RLS among the 190 Korean schizophrenic patients by the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Genotyping was performed for the 40bp VNTR in DAT1 gene using polymerase chain reaction. RESULTS: We separated the schizophrenic patients into 44 patients with RLS and 146 patients without RLS. The genotype and allele frequencies did not differ significantly between two groups. CONCLUSIONS: These results suggest that DAT1 gene 40bp VNTR is not associated with the antipsychotic-induced RLS in schizophrenia. To confirm these results, larger-scale association study is needed in the future.

Polymorphisms of the Interleukin - 6 Gene and Bone Mineral Density at Postmenopause in Korean Women / 대한내분비학회지

BACKGROUND: Interleukin-6 (IL-6) is one of the candidate cytokines to play an important role in bone loss followed by estrogen deficiency. Recently, the IL-6 VNTR (various number tandem repeats) genotype was reported to be associated with bone mineral density, raising the possibility that genotyping at this site might be of value in identifying women who are at risk for postmenopausal osteoporosis. To evaluate whether allelic variants in the gene encoding the polymorphism of VNTR located at the 3 flank of the IL-6 gene in Koreans were also the same as those of Caucasian, we analyzed the distribution pattern of the polymerase chain reaction product of the IL-6 gene. METHODS: The IL-6 VNTR were examined in 134 postmenopausal Korean women. Bone mineral densities were measured by DEXA (dual energy X-ray absorptiometry, Lunar Radiation, Madison, WI). RESULTS: The IL-6 VNTR polymorphism of Koreans was different from that of Caucasian, and four genotypes (KaKb, KbKb, KbKc and KbKd) were identified. The genotypes KaKb and KbKd were found only in one individual each and most Koreans had KbKb or KbKc genotypes. The overall prevalences of KbKb and KbKc genotypes were 76.9% Rlld 21.6%, respectively, and the distribution patterns of the genotypes were not different among normal, osteopenic and osteoporotic groups. The values of bone mineral density at the lumbar spine and femoral neck were not different between the frequent genotypes of KbKb and KbKc. Furthermore, the levels of alkaline phosphatase, osteocalcin and urinary deoxypyridinoline/creatinine were also not different between the two genotypes. CONCLUSION: There are ethnic differences in IL-6 VNTR polymorphism, and IL-6 VNTR polymorphism may not be associated with postmenopausal osteoporosis in Korean women. Our data suggest that the analysis of IL-6 VNTR polymorphism may not be helpful in detecting patients at risk of developing osteoporosis.

Association of Alcohol Dependence with the Dopamine Transporter Gene Polymorphism / 신경정신의학

OBJECTIVES: Alcoholism is known to be a heritable disease. It has been hypothesized that dopamineergic systems play an important heritable role in human behavor related to alcohol dependence, such as alcohol seeking. Therefore, genes involved in this pathway, including dopamine transporter(DAT1) which is responsible for taking released dopamine back up into presynaptic terminals and terminating dopaminergic activity, are potential candidate that may affect susceptibility to alcoholism. Analysis of a 40-base pair(bp)repeat(VNTR)in the 3'untranslated region of the DAT1 gene revealed variable number of the repeat ranging from 3 to 11 copies. Therefore, in the present study, we examined the association between alcoholism and VNTR polymorphism of DAT1. METHODS: Genomic DNA analysis with polymerase chain reaction(PCR)was used to identify the presence of a VNTR polymorphism. It was carried out within a group of 94 alcoholic patients and 113 normal controls. RESULTS: 1)There were no significant differences in allelic or genotype frequencies between the group of alcoholic patients and controls. 2)There were no significant differences in the first drinking age, onset age and latency of alcoholism according to DAT1 genotypes. 3)There was a significant difference in allelic frequencies between alcoholics with family history and those without family history. CONCLUSIONS: These results suggested that VNTR polymorphism of DAT1 is unlikely to be a factor in the genetic etiology of alcoholism, but might be related to familial transmission of alcoholism.

VNTR Polymorphism of the Tyrosine Hydroxylase in Bipolar Patients / 신경정신의학

OBJECTIVES: Tyrosine hydroxylase(TH) is a rate-limiting enzyme in the synthesis of catecholamines, and could be a candidate gene for causing the bipolar disorders. Therefore, we designed this study to investigate the association of the VNTR(variable number of tandem repeats) polymorphic locus in the first intron of the TH gene with bipolar disorders. METHODS: We typed VNTB polymorphic region of the TH gene using PCR in 115 bipolar patients and 85 normal controls. Four types of alleles(A, B, C, D) were typed according to the difference of the repeat(TCAT)6-9 number. The frequencies of allele and genotype were compared between patients and normal controls, and in patients and normal controls allelic frequencies were compared respectively in terms of family history of affective disorders and age of onset. RESULTS: 1) The allelic frequencies were significantly lower in type A, and significantly higher in type D in patient group compared to control group. The genotype frequencies were significantly higher in type BD in patient group than in control group. 2) In comparing the allelic frequencies among patient group with and without family history and control group, there were no significant differences between groups with and without family history, whereas patient group with family history showed lower significance in type A and higher significance in type D compared to control group. 3) In comparing the allelic frequencies among patient groups with early onset and late onset and control group, patient group with early onset showed higher significance in type D than patient group with late onset and showed lower significance in type A and higher significance in type D compared to control group. CONCLUSIONS: The authors conclude that the VNTR polymorphic region of the TH gene might be associated bipolar disorders, and type A and type D alleles might be susceptibility genes of bipolar disorder.