ABSTRACT
Background: Epidemiologic studies have shown a higher prevalenceof hypertriglyceridemia among patients with CHDthan among unaffected populations. Dozens of polymorphisms in different genesthat could have some effect on plasma TG levels havebeen analyzed. The most promising results are connected withvariants within the apolipoproteins (APO) APOA1/APOC3/ APOA4 gene cluster. Transgenic mice overexpressing human apolipoprotein A5decreased plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking APOA5 had four times as much plasma triglycerides as controls.The human APOA5 gene consistsof 4 exons and codes 369 aminoacidprotein, which is expressed almost exclusively in the liver.A minor allele of APOA5 (1259C, IVS3+476A and 1131C) which was independently associated with high plasma triglyceride levels in African-American, non Hispanic whites, Hispanic, Caucasians and Japanese were reported. Four polymorphisms in ApoA5 (1259T>C, IVS3+476G>A, S19W and 1131T>C) has been correlatedwith high TG levels in diabetic women. Materials and Methods: 162 people with MS for case group and 144 people for control group were selected in this study. MS was diagnosed according to IDF criteria and serum triglyceride, total cholesterol and HDL levels were determined. DNA from both case and control subjects were extracted from blood samples (20μL) using “G-spin™ Total DNA Extraction Kit”(iNtRON Biotechnology, Inc).The genotypes for fourpolymorphisms of ApoA5 were determined using a combination of PCR and sequence-specific oligonucleotide probes. Results: There were 304 total subjects included males 50.3% (153) and female 49.7% (151) in our study. The appearance of risk genotypes of 1177C>T, 1259T>C, IVS3+476G>A and 1131T>C polymorphisms in ApoA5 gene were higher in MS group than control group.Serum levels of triglycerides and total cholesterol differed significantly (pC genotypes. Conclusion: TAG and TC level was higher in people with 1131T>C-CC genotype than other genotypes in both groups (p=0.010, p=0.001). We determined that the odds ratio for the hypertriglyceridemia was 5.98 for ApoA5-1131T>C CC-genotype carriers.
ABSTRACT
Background. A large number of longitudinal studies indicate significantly increased risk of cardiovascular events and death in people with the MetSyn and high plasma levels of triglycerides are an independent risk factor for the development of cardiovascular disease. Apolipoprotein A5 (APOA5) gene, a new member of the APOA1/C3/A4 gene cluster, was identified by comparative sequencing of human and mice DNA by Pennacchio and co-workers in 2001. Since this discovery, variants of ApoA5 gene have been independently assiociated with level of plasma triglyceride in many countries. Human ApoA5 is expressed in the liver then appears in plasma in association with VLDL and HDL and plays a major role in TG catabolism. Variant at ApoA5 gene locus, 1177C>T is located in 3’ UTR which often contains regulatory regions that influence post-transcriptional gene expression. One alteration can be responsible for the altered expression of many genes. Materials and Methods. 152 people with MS for case group and 152 people for control group were selected in this study. MS was diagnosed according to IDF criteria and serum triglyceride levels were determined. DNA from both case and control subjects were extracted from blood samples (200 ml) using “G-spin™ Total DNA Extraction Kit”(iNtRON Biotechnology, Inc). To detect the 1177C>T variation of ApoA5 gene, using High Pure PCR Template Preparation Kits, a forward primer 5’-CTCTGAGCCTCTAGCATGGTTGAGT- 3’ and the mismatch reverse primer 5’-GAGCATTCCCAAATGAGCAC-3’ were used to create the HinfI restriction site. Results. There were 304 total subjects included males 50.3% (153) and female 49.7% (151) in our study. Incident of CC genotype was 71.1% (216), CT genotype was 25% (76) and TT genotype was 3.9%, TAG level was higher in males than females in both groups (p=0.016, ð=0.001) for CC genotype and also, higher with MS in males for CT genotype (p=). But, TAG level was no significant difference among three genotypes in group with MS subjects (male p=0.236, female p=0.881). Conclusion: The TT genotype of the ApoA5 gene 1177C>T polymorphism frequency was 2.9% in control subjects and 4.9% in subjects with MS. However, TG level was not differ in both groups for TT genotype, TAG level in males was higher compared with females (p=0.016 in control, p=0.001 in group with MS).
ABSTRACT
Background: Discrepancies in the sensitivity to biological effects of the androgens, exerted through the binding of the hormone to the androgen receptor (AR), may also be involved in the inter-individual variation of T as well as in age related decline. The human androgen receptor (AR), located on chromosome Xq11-12, is a transcription factor regulating the development of male reproductive organs in the fetus and secondary sex characteristics at puberty in response to testosterone (T) and 5a-dihydrotestosterone (DHT). The AR contains two polymorphic regions, the (CAG)nCAA repeat encoding polyglutamine, and the (GGT)3GGG(GGT)2(GGC)n repeat encoding polyglycine, commonly referred to as the CAG and GGN repeats respectively. The aim of this study is to investigate the effect of the human androgen receptor genes CAG and GGN repeat polymorphisms in relation with androgen level.Materials and Methods: Sample collection: 180 male, the medical data of these volunteers were obtained and determined some androgen hormones at first phase of study in 2010-2011 (total testosterone (TT), free testosterone (FT) and bioavailable testosterone (BAT)). To determine CAG/GGN repeats length in exon of androgen receptor gene, using frozen serum as a source of deoxyribonucleic acid (DNA). DNA was extracted from blood samples (200 ml) using High PurePCR Template Preparation Kits.Results: The 180 men whose age is at least 40 were involved in our research and their average age was 55.1±10.3. The 46.7% (84) of the participants presents CAG gene, the 6.1% (11) of the participants presents GGN gene while the 25.5% (46) of the participants presents both CAG and GGN genes. However, the 21.7% of 39 men not presents CAG and GGN genes.Conclusion: The free testosterone level was significantly decreasing with aging. However, the appearance of CAG gene polymorphism was significantly higher in more aged people. Decline of free testosterone level in participants with CAG and [CAG+GGN] combined form was stronger than in people with GGN gene polymorphism and CAG, GGN both undetected people. But the level of bioavailable testosterone was decreasing with aging and the appearance of CAG gene polymorphism (r=-0.425, p=0.01) and [CAG+GGN] combined form (r=-0.491, p=0.028) was also increasing.