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Which genes make women? Significant nucleotidic variation in Mayer-Rokitansky-Kuster-Hauser syndrome patients
POSTER PRESENTATIONS
smoke into highly reactive epoxides. Once released outside the cell, MPO may damage the surrounding tissue through the oxidant properties of its products. A p o l y m o r p h i s m in p r o m o t e r region of MPO (463G>A) has been found to be associated with lung cancer. This p o l y m o r p h i s m is also responsible for the creation of a novel estrogen receptor binding site, through w h i c h estrogens may increase MPO A allele p r o m o t e r activity. This may induce gender specific differences in lung cancer risk. Aims of this study were to evaluate the association between MPO p o l y m o r p h i s m and lung cancer, and the possible interactions between MPO polymorphism, gender, and age. We performed a pooled analysis of 8 studies (2905 cases and 3085 controls) from the GSEC data-base. The MPO A allele was protective towards lung cancer (OR for A/G+A/A vs G/G = 0.80, 95% CI, 0.710.90), after adjusting for smoking and race. This effect was still present in males (OR = 0.84, 95% CI, 0.74-0.95), but n o t in females (OR = 0.91, 95% CI, 0.75-1.09). A significant interaction between MPO G/A genotype and age was found a m o n g females, with MPO being protective in younger (OR = 0.4, 95% CI, 0.17-0.94), but not in older w o m e n (OR = 1.07, 95% CI, 0.64-1.77). This analysis suggests that MPO may modify the relationship between estrogens and lung cancer. The significant protective effect of the MPO variant allele disappeared in older females, where exposure to estrogen has been longer in time, but has been discontinued.
26
Which Genes Make Women? Significant Nucleotidic Variation in Mayer-RokitanskyKuster-Hauser Syndrome Patients M i h o Fujiil; Akiyo Sugai2; Kenichiro Ikuma3; Toshiaki Endol; a n d Tsuyoshi Saito 1
i Sapporo Medical University, Sapporo, Japan; 2Tenshi Hospital, Caress Alliance Medical Corporation, Sapporo, Japan; and 3Takarazuka City Hospital, Japan In mammals, several transcription factors such as Ad4BP/SF1, Dax-1, Sox9, Wt-1, Emx-2, and GATA-4 are indispensable for gonad differentiation. We have analyzed several genes whose mutation may impair the development and maintenance of the female genitalia. Fifteen female patients were included in the study. Eight fulfilled the criteria for diagnosis of MRKH anomaly, 6 were vaginal absence cases with and without uterine anomaly, and 1 was gonadal dysgenesis case. The patient's DNA was extracted according to standard procedures from peripheral leucocytes. PCR was carried out. Products were purified and used to analyze for DNA sequence variation. A total of 15 control chromosomes were tested. Direct DNA sequencing was used to screen the WNT4, DAX-1, and Sox9 genes for nucleotide variation. No significant variation was observed in the coding region of the genes. Since direct DNA sequencing analysis is regarded as the most efficient strategy for detection of mutations, these genes can be excluded as a genetic cause of MRKH anomaly. Although factors involved in male sexual differentiation including roles of Sry, Sox9, Daxl, or mullerian inhibitory substance (MIS) have been well studied, the pathways that regulate female sexual differentiation remain incompletely defined. We have tried to show some transcriptional genes that suppress MIS, but could not find any single gene mutations that differentiate female gonad. We turn to find some cascades which regulate roles of genes that play in female gonad development.
27
Is the Coronary Risk Different, in our Men and Women? V.J. Gavara Palomarl; C. Ariza Copadol; A.L. Garcia Gonzalez2; S. M a r t i n Sotol; C. Lopez Marquezl; E. O r d o n e z Ordonezl; F. Aguera Menguall; A. Barba J i m e n e z l ; A. N i a n g Fernandez1; R. H e r n a n d e z Calerl; a n d M. Soto M a r t i n e z 1
iPrimary Care Center: Isaac Peral, Cartagena SMS, Spain; and 2Unidad Docente Gerencia de Cartagena SMS, Spain A i m : To know if there are differences with respect to coronary risk factors distribution, and coronary risk level, between our m e n and w o m e n with hypercholesterolemia, according to NCEP III-ATP III recommendations. P a t i e n t s a n d m e t h o d : Descriptive, cross-sectional and retrospective study. N = 248. Urban health center. Patients with a diagnosis of hypercholesterolemia and more than one lipid profile blood test carried out from 1-1-2002 to 31-12-2003. Systematic sampling, accuracy +6%, and confidence interval 95%. M e a s u r e m e n t s : Coronary risk factors distribution in m e n and women, cardiovascular disease presence or equivalent (DIM), and coronary level in both genders. Bi-variant and descriptive statistic analysis. Results: Prevalence of smoking (31.5%) and HDL-C <40 mg/dL (14%) is higher in men (P = 0.02). W o m e n have higher prevalence of hypertension (65.4%; P = 0.02) and HDL-C >60 mg/dL (48.7%; P < 0.001). Peripheral arteriopathy (8.9%) and coronary disease (18.5%) are higher in men (P = 0.005 and P = 0.002, respectively). There is no significant difference with respect to cerebrovascular disease (cerebral thromboembolism or hemorrhage) and diabetes. We have found high coronary risk levels in both men (66.4%) and w o m e n (42.3%) (P = 0.0001), moderate coronary risk in 16.3% m e n and 5.2% w o m e n (P = 0.001), and low coronary risk 33.7% in m e n and 53.8% in women. C o n c l u s i o n s : We must improve cardiovascular risk factors in our m e n with hypercholesterolemia, especially with respect to smoking and low HDL-C levels, because they have higher coronary risk than women. Otherwise we must improve hypertension control in our w o m e n with hypercholesterolemia. 28
The Impact of Gender Differences on Serum Total Immunoglobulin E (IgE) and Histamine Levels in Migraine Patients Without Aura Parisa Gazerani; a n d Lars Arendt-Nielsen
Center for Sensory-MotorInteraction (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark Migraine is a c o m m o n disorder with higher prevalence in females. Mechanism(s) underlying migraine and its sexrelated etiology remains partly unclear. Higher female prevalence can be attributed to multiple factors such as genes, biological, hormonal, socio-cultural, and environmental. We investigated the impact of gender differences on i m m u n o g l o b u l i n E (IgE) and h i s t a m i n e levels in migraine patients. Seventy-five migraine patients (58 F, 17 M; 18-58 year) without aura were studied. Serum samples were collected during attack and remission. Healthy volunteers (N = 45) of b o t h genders, without headache or allergy, served as control group. Serum total IgE and histamine levels were measured by enzyme-linked i m m u n o s o r b e n t assay and fluorimetry. Analysis of data revealed that 49.33% of
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smoke into highly reactive epoxides. Once released outside the cell, MPO may damage the surrounding tissue through the oxidant properties of its products. A p o l y m o r p h i s m in p r o m o t e r region of MPO (463G>A) has been found to be associated with lung cancer. This p o l y m o r p h i s m is also responsible for the creation of a novel estrogen receptor binding site, through w h i c h estrogens may increase MPO A allele p r o m o t e r activity. This may induce gender specific differences in lung cancer risk. Aims of this study were to evaluate the association between MPO p o l y m o r p h i s m and lung cancer, and the possible interactions between MPO polymorphism, gender, and age. We performed a pooled analysis of 8 studies (2905 cases and 3085 controls) from the GSEC data-base. The MPO A allele was protective towards lung cancer (OR for A/G+A/A vs G/G = 0.80, 95% CI, 0.710.90), after adjusting for smoking and race. This effect was still present in males (OR = 0.84, 95% CI, 0.74-0.95), but n o t in females (OR = 0.91, 95% CI, 0.75-1.09). A significant interaction between MPO G/A genotype and age was found a m o n g females, with MPO being protective in younger (OR = 0.4, 95% CI, 0.17-0.94), but not in older w o m e n (OR = 1.07, 95% CI, 0.64-1.77). This analysis suggests that MPO may modify the relationship between estrogens and lung cancer. The significant protective effect of the MPO variant allele disappeared in older females, where exposure to estrogen has been longer in time, but has been discontinued.
26
Which Genes Make Women? Significant Nucleotidic Variation in Mayer-RokitanskyKuster-Hauser Syndrome Patients M i h o Fujiil; Akiyo Sugai2; Kenichiro Ikuma3; Toshiaki Endol; a n d Tsuyoshi Saito 1
i Sapporo Medical University, Sapporo, Japan; 2Tenshi Hospital, Caress Alliance Medical Corporation, Sapporo, Japan; and 3Takarazuka City Hospital, Japan In mammals, several transcription factors such as Ad4BP/SF1, Dax-1, Sox9, Wt-1, Emx-2, and GATA-4 are indispensable for gonad differentiation. We have analyzed several genes whose mutation may impair the development and maintenance of the female genitalia. Fifteen female patients were included in the study. Eight fulfilled the criteria for diagnosis of MRKH anomaly, 6 were vaginal absence cases with and without uterine anomaly, and 1 was gonadal dysgenesis case. The patient's DNA was extracted according to standard procedures from peripheral leucocytes. PCR was carried out. Products were purified and used to analyze for DNA sequence variation. A total of 15 control chromosomes were tested. Direct DNA sequencing was used to screen the WNT4, DAX-1, and Sox9 genes for nucleotide variation. No significant variation was observed in the coding region of the genes. Since direct DNA sequencing analysis is regarded as the most efficient strategy for detection of mutations, these genes can be excluded as a genetic cause of MRKH anomaly. Although factors involved in male sexual differentiation including roles of Sry, Sox9, Daxl, or mullerian inhibitory substance (MIS) have been well studied, the pathways that regulate female sexual differentiation remain incompletely defined. We have tried to show some transcriptional genes that suppress MIS, but could not find any single gene mutations that differentiate female gonad. We turn to find some cascades which regulate roles of genes that play in female gonad development.
27
Is the Coronary Risk Different, in our Men and Women? V.J. Gavara Palomarl; C. Ariza Copadol; A.L. Garcia Gonzalez2; S. M a r t i n Sotol; C. Lopez Marquezl; E. O r d o n e z Ordonezl; F. Aguera Menguall; A. Barba J i m e n e z l ; A. N i a n g Fernandez1; R. H e r n a n d e z Calerl; a n d M. Soto M a r t i n e z 1
iPrimary Care Center: Isaac Peral, Cartagena SMS, Spain; and 2Unidad Docente Gerencia de Cartagena SMS, Spain A i m : To know if there are differences with respect to coronary risk factors distribution, and coronary risk level, between our m e n and w o m e n with hypercholesterolemia, according to NCEP III-ATP III recommendations. P a t i e n t s a n d m e t h o d : Descriptive, cross-sectional and retrospective study. N = 248. Urban health center. Patients with a diagnosis of hypercholesterolemia and more than one lipid profile blood test carried out from 1-1-2002 to 31-12-2003. Systematic sampling, accuracy +6%, and confidence interval 95%. M e a s u r e m e n t s : Coronary risk factors distribution in m e n and women, cardiovascular disease presence or equivalent (DIM), and coronary level in both genders. Bi-variant and descriptive statistic analysis. Results: Prevalence of smoking (31.5%) and HDL-C <40 mg/dL (14%) is higher in men (P = 0.02). W o m e n have higher prevalence of hypertension (65.4%; P = 0.02) and HDL-C >60 mg/dL (48.7%; P < 0.001). Peripheral arteriopathy (8.9%) and coronary disease (18.5%) are higher in men (P = 0.005 and P = 0.002, respectively). There is no significant difference with respect to cerebrovascular disease (cerebral thromboembolism or hemorrhage) and diabetes. We have found high coronary risk levels in both men (66.4%) and w o m e n (42.3%) (P = 0.0001), moderate coronary risk in 16.3% m e n and 5.2% w o m e n (P = 0.001), and low coronary risk 33.7% in m e n and 53.8% in women. C o n c l u s i o n s : We must improve cardiovascular risk factors in our m e n with hypercholesterolemia, especially with respect to smoking and low HDL-C levels, because they have higher coronary risk than women. Otherwise we must improve hypertension control in our w o m e n with hypercholesterolemia. 28
The Impact of Gender Differences on Serum Total Immunoglobulin E (IgE) and Histamine Levels in Migraine Patients Without Aura Parisa Gazerani; a n d Lars Arendt-Nielsen
Center for Sensory-MotorInteraction (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark Migraine is a c o m m o n disorder with higher prevalence in females. Mechanism(s) underlying migraine and its sexrelated etiology remains partly unclear. Higher female prevalence can be attributed to multiple factors such as genes, biological, hormonal, socio-cultural, and environmental. We investigated the impact of gender differences on i m m u n o g l o b u l i n E (IgE) and h i s t a m i n e levels in migraine patients. Seventy-five migraine patients (58 F, 17 M; 18-58 year) without aura were studied. Serum samples were collected during attack and remission. Healthy volunteers (N = 45) of b o t h genders, without headache or allergy, served as control group. Serum total IgE and histamine levels were measured by enzyme-linked i m m u n o s o r b e n t assay and fluorimetry. Analysis of data revealed that 49.33% of
$51