Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.

The genetic predisposition to addiction to opioids and other substances is transmitted as a complex genetic trait, which investigators are attempting to characterize using genetic linkage and association. We now report a high-density genome-wide linkage study of opioid dependence. We ascertained 305 DSM-IV opioid dependent affected sibling pairs from an ethnically mixed population of methadone maintained subjects and genotyped their DNA using Affymetrix 10K v2 arrays. Analysis with MERLIN identified a region on chromosome 14q with a non-parametric lod (NPL) of 3.30. Secondary analyses indicated that this locus was relatively specific to the self-identified Puerto Rican subset, as the NPL increased from 3.30 to 5.00 (NPL(Caucasian) = 0.05 and NPL(African Amer.) = 0.15). The 14q peak encompasses the NRXN3 gene (neurexin 3), which was previously identified as a potential candidate gene for addiction. Secondary analyses also identified several regions with gender-specific NPL scores greater than 2.00. The most significant was a peak on (10q) that increased from 0.90 to 3.22 when only males were considered (NPL(female) = 0.05). Our linkage data suggest specific chromosomal loci for future fine-mapping genetic analysis and support the hypothesis that ethnic and gender specific genes underlie addiction susceptibility.

No abstract

Objective: To investigate the prevalence of 4G5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in polycystic ovary syndrome (PCOS) and its functional significance. Design: Case-control study. Methods: We studied 98 patients and 64 controls. Body mass index (BMI) and waist-to-hip (WHR) ratio were determined. Blood samples were obtained for DNA analysis. PAI-1 plasma levels, serum total testosterone, fasting insulin and fasting glucose were measured and the glucose-to-insulin ratio was estimated in all subjects.Results: There was a statistically significant difference in the distribution of PAI-1 gene variations among the groups. The PCOS group had significantly higher 4G/4G and 4G/5G combinations than the control group, whereas there were significantly less 5G/5G. Among the PCOS women, 39.8% had the genotype 4G/4G, 39.8% 4G/5G and 20.4% 5G/5G. From the control group, 20.3% had genotype 4G/4G, 28.1% 4G/5G and 51.6% 5G/5G. In the 4G/4G genotype subgroup 75% were PCOS and 25% were controls, in the 4G/5G were 68.42% and 31.58% and in the 5G/5G were 31.58% and 62.26% respectively. The population of PCOS women had significantly higher PAI-1 levels, WHR, total testosterone, and fasting glucose than the population of controls. Conclusions: 1)The genotypic subtypes 4G/4G and 4G/5G, in PCOS, were present with a statistically higher frequency compared with controls. 2)PCOS women have higher levels of PAI-1 compared with the control group. 3)The presence of the 4G allele in PAI-1 promoter region of the gene further increases the PAI-1 levels. 150 793-798 European Journal of Endocrinology