Filiz Guclu-Geyik

Gender-specific associations of the APOA1 -75G>A polymorphism with several metabolic syndrome components in Turkish adults.

BACKGROUND Variations in the apolipoprotein A-1 (APOA1) gene, a determinant of plasma high-density lipoprotein cholesterol (HDL-C) and apoA-I levels, may contribute to cardiovascular diseases. We evaluated the effects of a promoter polymorphism (-75G>A) in the APOA1 gene on metabolic syndrome (MetS) components in a Turkish population sample. METHODS Randomly selected 1515 Turkish adults (age 49.9±11.8 years, 785 females) were genotyped for -75G>A polymorphism using hybridization probes in Real-Time PCR LC480 device. MetS and atherogenic dyslipidemia were defined using the criteria of ATP III. RESULTS The -75AA genotype prevailed in 3.9% of men and 2.4% of women, and was independently associated with significantly higher HDL-C concentrations. Independent associations with the -75GA genotype existed only in men: higher diastolic and systolic blood pressure (BP) levels (p<0.05) were observed in male -75GA heterozygotes. Logistic regression revealed that the GA genotype confers elevated risk for atherogenic dyslipidemia (OR=1.57, 95% Cl 1.06-2.3) after adjustment for associated risk factors. Independent associations with atherogenic dyslipidemia or elevated BP did not emerge in women. CONCLUSION APOA1 -75G>A polymorphism is independently related to HDL-C concentrations. Independent associations of the -75GA genotype with elevated BP and atherogenic dyslipidemia were confined to men. These gender-modulated associations suggest novel gene-gender-environmental interactions.

Sex- and Obesity-specific Association of Aromatase (CYP19A1) Gene Variant with Apolipoprotein B and Hypertension

BACKGROUND AND AIMS Gender differences in cardiovascular disease risk have been attributed to sex hormones. The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus affects body fat distribution and regulation. We examined the relationship between polymorphism of the CYP19A1 gene and lipoproteins, body mass index (BMI), insulin levels and HOMA index. METHODS Randomly selected 2250 Turkish adults (aged 49.7 ± 11.9 years; 48.6% males) were genotyped for CYP19A1 rs10046 polymorphism using hybridization probes in Real-Time PCR LC480 device. RESULTS Distribution of the CYP19A1 rs10046 polymorphism was 28% (n = 630), 48.3 % (n = 1085) and 23.7% (n = 535) for the CC, CT and TT genotypes, respectively, and the T allele frequency was 0.48. In relation to apolipoprotein (apo)B levels, C homozygosity was associated with higher apoB in non-obese females, contrasting to being so in obese males only, and further in postmenopausal females. CC genotype in females was associated in linear regression analysis by 7.2 ± 3.3 mg/dL higher apoB than CT + TT genotypes, independent of age and BMI. Among premenopausal females, insulin levels (p = 0.007), BMI (p = 0.05) and HOMA index (p = 0.034) were higher in C homozygotes than in T-allele carriers. However, CYP19A1 TT genotype contributed to hypertension at an OR 1.80 (95% CI 1.12-2.91), independently of age, BMI and other confounders, in males alone. CONCLUSION The CYP19A1 rs10046 polymorphism is associated with cardiovascular risk factors such as circulating apoB, insulin resistance and hypertension in a sex- and obesity-specific manner.

Prevalence of Prader-Willi Syndrome among Infants with Hypotonia

OBJECTIVE To investigate the prevalence of Prader-Willi syndrome (PWS) in infants with hypotonia between the ages of 0 and 2 years. STUDY DESIGN Karyotyping studies were performed in all infants with hypotonia. The study group was composed of infants with hypotonia for whom the karyotyping was found to be normal. Fluorescence in situ hybridization and methylation analysis were performed simultaneously in the study group. Molecular studies for uniparental disomy were undertaken in the patients without deletions with an abnormal methylation pattern. RESULTS Sixty-five infants with hypotonia with a mean age of 8 months were enrolled. A deletion was detected in 6 patients by fluorescence in situ hybridization analysis. Only 1 patient had no deletion but had an abnormal methylation pattern. A maternal uniparental disomy was observed in this patient. PWS was diagnosed in 10.7 % (7/65) of the infants with hypotonia. CONCLUSION The prevalence of PWS syndrome is high among infants with hypotonia. PWS should be considered by pediatricians and neonatologists in the differential diagnosis of all newborns with hypotonia. Early diagnosis of PWS is important for the management of these patients.

Gender- and obesity-specific effect of apolipoprotein C3 gene (APOC3) –482C>T polymorphism on triglyceride concentration in Turkish adults

Abstract Background: Apolipoprotein C3 (APOC3) gene polymorphisms are associated with cardiometabolic risk factors, varying in ethnicities. This study aimed to investigate such association between the APOC3 –482C>T polymorphism and cardiometabolic risk factors in the turkish adult risk factor (TARF) study cohort, stratifying by gender and obesity. Methods: Randomly selected 1548 individuals (757 male and 791 female, mean age 49.9±11.8 years) were genotyped for –482C>T polymorphism using hybridization probes in a Real-Time PCR LC480 device. Results: The –482TT genotype prevailed 9.9% in men and 11.5% in women. Association between 482C>T polymorphism and dyslipidemia (p=0.036, OR=1.42, 95%Cl=1.02–1.97) was found only in men. Analysis of variance showed that anthropometric and metabolic variables were not differently distributed in APOC3 –482C>T genotypes in the study population. In relation to dyslipidemia and obesity, the –482C>T polymorphism showed significant gender-by-genotype interactions (p<0.01). When the study population was stratified according to gender and obesity, homozygotes for the T allele were associated strongly with (by 45%) elevated fasting triglyceride concentrations in obese men (p=0.009) and homeostatic model assessment (HOMA) index in non-obese women (p=0.013). Furthermore, in the same subgroups, the associations of the fasting triglyceride concentrations and HOMA index with the TT genotype remained after adjustment for risk factors (p<0.05). Conclusions: APOC3 –482TT genotype is independently associated with elevated fasting triglyceride concentrations in obese men. Presence of obesity seems to be required for this genotype to induce markedly elevated triglycerides. Furthermore, it is associated with the dyslipidemia in men, without requirement of obesity.