Long-long Genotype Research Articles

Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as “short/short (SS)”, “short-long (SL)” and “long-long (LL)”. The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD.

PWE-033 Promoter Region Variations in The Glutaminase Gene as A Risk Factor for The Development Hepatic Encephalopathy in Patients with Cirrhosis: Abstract PWE-033 Table 1

Introduction Hepatic encephalopathy (HE) is the commonest complication of cirrhosis but its development is not invariable; thus approximately 20% of individuals remain free of neuropsychiatric complications and patients with minimal HE do not invariably develop overt HE. It is possible that genetic factors, most likely resulting in deregulation of ammonia metabolism, might determine an individual’s susceptibility to develop this complication. In 2010, Romero-Gomez and colleagues, 1 identified a functional microsatellite consisting of GCA repeats near the promoter region of the glutaminase gene, GLS1, and proposed that patients with cirrhosis who were homozygous for the long microsatellite allele were more likely to develop overt HE. The aim of this study was to further investigate the association between GLS1 promoter microsatellite variants and HE. Methods The study population comprised 110 patients with cirrhosis, of British/Irish ancestry, in whom neuropsychiatic status had remained stable during monitoring for a minimum of 5 years, except in those treated for overt HE. Patients were classified using clinical, neurophysiological and neuropsychometric variables as: unimpaired (51; 46%) or as having minimal (24; 22%) or overt (35; 32%) HE. The control population comprised 325 ancestrally-matched healthy controls. DNA was genotyped using gel electrophoresis and verified by Sanger sequencing. Alleles were stratified as long (≥14 GCA repeats) or short ( Results There were no significant differences in allele frequencies or genotype distributions between cases and controls. The proportion of long-short heterozygotes was significantly higher in the unimpaired patients (62.7%) than in those with either minimal HE (37.5%) or overt HE (37.1%) (p = 0.029; Table). Conclusion There was no evidence that the long-long genotype is a risk factor for HE in the present study. However, there was evidence of possible heterozygote advantage resulting in significant protection against the development of this syndrome. More studies are needed to confirm or refute these findings. Reference 1 Romero-Gomez M, et al . Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med 2010; 153 :281–8. Disclosure of Interest None Declared

Microsatellite polymorphism in the heme oxygenase-1 promoter is associated with nonsevere and late-onset preeclampsia.

Preeclampsia is a serious and phenotypically heterogeneous vascular pregnancy disorder. Heme oxygenase-1 (HO-1) is a stress response enzyme that may protect the maternal endothelium and facilitate adequate metabolic adaptation to pregnancy by its antioxidant and anti-inflammatory functions. HO-1 stress response is modulated by HO-1 gene (HMOX1) polymorphisms. Individuals with the long allele of a guanine-thymine (GTn) microsatellite repeat located in the promoter region of HMOX1 have a higher risk of cardiometabolic diseases compared with those with the short allele. We investigated whether the long GTn allele of HMOX1 is associated with subtypes of preeclampsia. The GTn repeat was genotyped in 759 patients and in 779 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort using DNA fragment analysis. In subtype analyses, the long-long (LL) genotype was associated with nonsevere (additive model: odds ratio [OR], 1.94; 95% confidence interval [CI], 1.13-3.31; recessive model: OR, 1.39; 95% CI, 1.02-1.89) and late-onset (additive model: OR, 1.44; 95% CI, 1.02-2.05; recessive model: OR, 1.28; 95% CI, 1.02-1.59) preeclampsia and with preeclampsia without a small-for-gestational-age infant (recessive model: OR, 1.27; 95% CI, 1.02-1.58). The long allele was associated with nonsevere (OR, 1.35; 95% CI, 1.07-1.70) and late-onset (OR, 1.21; 95% CI, 1.03-1.42) preeclampsia and with preeclampsia without a small-for-gestational-age infant (OR, 1.19; 95% CI, 1.02-1.40). Moreover, both the LL genotype and the long allele were associated with preeclampsia in women who had smoked during pregnancy. In conclusion, the GTn long allele seems to predispose to late-onset, less severe form of preeclampsia. This finding supports the role of HO-1 in the pathogenesis of preeclampsia and suggests that the HO-1 pathway may provide a potential target for the treatment of preeclampsia.

Arginine Vasopressin 1a Receptor (AVPR1a) RS3 Repeat Polymorphism Associated with Entrepreneurship

Background: Entrepreneurship is crucial to the creation and development of every industry, and considerable work in economics, psychology, management, and other fields of social science has been devoted to analyzing characteristics of these individuals. Twin studies suggest that entrepreneurship has a genetic component, but so far no specific genes have been robustly identified. Methodology/Principal Findings: In a sample of 135 highly accomplished managers, we examine the frequencies of three genotypes: the long-repeat genotype of the RS3 microsatellite in the arginine vasopressin 1a receptor promoter region (AVPR1a), the 7-repeat genotype of the dopamine D4 receptor (DRD4), and the low-activity Monoamine Oxidase A (MAOA) genotype. We find that individuals who have founded more companies are significantly more likely to be homozygous for the long-repeat allele of AVPR1a. Furthermore, even among individuals who founded fewer companies, we find a higher frequency of the long-long genotype in our sample compared to data reported in outside studies not related to entrepreneurship. Conversely, no such relationship with entrepreneurship is observed for DRD4 or MAOA. Conclusions: The genetic associations (and lack thereof) reported here identify AVPR1a and not DRD4 or MAOA as a potential candidate for future research into the genetic underpinnings of entrepreneurship. However, our results should be interpreted with caution given the sample size and the prevalence of false positives in this literature.

Editorial: Identifying the genetic and environmental influences on psychological outcomes

Editorial: Identifying the genetic and environmental influences on psychological outcomes

Dopamine D4 receptor gene and severity of dependence

Family, twin and adoption studies demonstrate that substance dependence is determined partially by genes. Recent studies in opiate-dependent subjects have found a significant excess of the long-long (LL) allele of the 48bp repeat in the coding sequence of the DRD4 gene. This study examined this association further in a sample of 60 opiate dependent, 51 alcohol-dependent and 64 normal, healthy control subjects. No significant association between the polymorphism at DRD4 and opiate or alcohol abuse was found. However, results yielded a significant main effect on severity of dependence, demonstrating that individuals with the LL allele rated their severity of dependence significantly higher than those who had the short-short (SS) allele :[F(2, 101) = 5.0, p < 0.01]. This study suggests that the DRD4 gene does not directly influence vulnerability to substance dependence, but that possession of the LL genotype significantly increases severity of dependence.