Q192R polymorphism in the PON1 gene and nasal polyp in a Turkish population

The pathogenesis of nasal polyps is not completely understood. Oxidative damage contributes to polyp formation in the nasal mucosa. The paraoxonase 1 (PON1) enzyme is an important liver enzyme with high antioxidant activity. In this study, we investigated the correlation between Q192R genotypic polymorphism of the PON1 enzyme and nasal‐polyp disease. The study examined 62 nasal‐polyp patients and 88 controls. PON1 Q192R polymorphism was determined using polymerase chain reaction‐restriction fragment length polymorphism. The genotype distribution of the PON1 gene was significantly different between nasal‐polyp patients (QQ = 69.35%, QR = 25.81%, RR = 4.83%) and healthy controls (QQ = 52.27%, QR = 44.31%, RR = 3.40%). Our results suggest that the PON1 QQ genotype (odds ratio [OR] = 2.066, P = .036) is associated with a higher risk of developing the nasal‐polyp disease while QR genotype (OR = 0.437, P = .021) showed a lower risk.     

A preliminary study of human paraoxonase and PON 1 L/M55–PON 1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease

Paraoxonase 1 (PON 1) is a high‐density lipoprotein (HDL)‐associated enzyme with antioxidant function protecting low‐density lipoprotein (LDL) from oxidation. PON 1 has two amino acid polymorphisms in coding region; L/M 55 and Q/R 192. These polymorphisms modulate paraoxonase activity of the enzyme. PON 1 activity decreases in coronary artery disease (CAD). In the present study, distribution of PON 1 L/M 55 and Q/R 192 polymorphisms and the effect of these polymorphisms on the activities of PON 1, and on the severity of CAD in 277 CAD (+) patient and 92 CAD (?) subjects were examined. PON 1 L/M 55 and Q/R 192 genotypes were determined by PCR, RFLP and agarose gel electrophoresis techniques. Genotype distributions and allele frequencies for PON 1 Q/R 192 polymorphism were not significantly different between controls and CAD (+) patient group (p > 0.05), but in genotype and allele distribution of PON 1 L/M55 polymorphism, there was significantly difference among groups (p < 0.05). Genotype distributions for both polymorphisms were not significantly different between subgroups of single‐vessel disease (SVD), double‐vessel disease (DVD) and triple‐vessel disease (TVD). Serum PON 1 activity was lower in CAD (+) group than in controls and this was also statistically significant (p < 0.001). In both groups, the highest PON activities were detected in LL and RR genotypes. In summary, our results suggest that there is an association between the PON 1 L/M 55 polymorphism of paraoxonase and CAD in Turkish patients but not with PON 1 Q/R 192 polymorphism. However, it is hard to correlate these polymorphisms and severity of CAD. Copyright © 2009 John Wiley & Sons, Ltd.     

Paraoxonase 55 and 192 polymorphism and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin dependent diabetes mellitus

We investigated the effect of PON 55 and PON 192 polymorphisms on serum PON1 activity and lipid profiles in 213 non-insulin dependent diabetes mellitus (NIDDM) individuals and 116 non-diabetic controls among Turkish subjects. The distribution of PON 55/192 gene polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum lipid levels were measured enzymically. PON activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON 55 and 192 genotype distribution was similar in patients and controls and paraoxonase activity was generally lower in diabetics than in control subjects. We showed that PON 55 and 192 genotypes have a major effect on serum PON activity. PON 192 BB homozygotes had significantly higher PON activity than AA and AB genotypes among the control and NIDDM populations (p<0.001). PON 55 MM homozygotes had significantly lower PON activity than did LL and LM genotypes in control and NIDDM populations (p<0.05). The PON1 55 and 192 polymorphisms did not consistently influence the serum lipid profiles in either population. In conclusion, our results suggest that the paraoxonase activities are affected by PON1 genetic variability in Turkish NIDDM patients and controls.     

Paraoxonase 1 gene polymorphisms, paraoxonase/arylesterase activities and oxidized low-density lipoprotein levels in patients with migraine

The vascular endothelial dysfunction has been implicated in the pathogenesis of migraine. Oxidized low‐density lipoprotein (ox‐LDL) may impair endothelial function. Paraoxonase‐1 (PON‐1) prevents oxidative modification of LDL cholesterol (LDL‐C). So we investigated serum PON‐1 and arylesterase (ARE) activities, PON‐1 55 L/M and 192Q/R polymorphisms and the serum lipid profile in patients with migraine. Biochemical parameters and PON‐1 polymorphism analyses were assessed in 104 patients with migraine and 86 healthy subjects. Ox‐LDL was detected by ELISA, and polymorphisms were determined using PCR–restriction fragment length polymorphism analysis. Patients with migraine had lower PON‐1 and ARE activities (p < 0·001, for both) and higher ox‐LDL and LDL‐C levels (p < 0·001, for both) and ox‐LDL: LDL‐C ratio (p < 0·005) than the controls. The genotype distribution and the allele frequencies for PON‐1 55 L/M and 192Q/R polymorphisms were not different among the study populations. The results of our current study indicate that migrainous patients have decreased serum PON‐1 and ARE activities and increased serum ox‐LDL levels, which may have a clinical importance in the treatment of migraine. Copyright © 2011 John Wiley & Sons, Ltd.     

Paraoxonase 1 (PON1) and its relationship to lipid variables, age and gender in healthy volunteers

Recent studies implied that low-density lipoprotein (LDL) modified predominantly by oxidation or glycation, significantly contributes to the formation of atherosclerotic lesions. In contrast to oxidized LDL (ox-LDL), high-density lipoprotein (HDL) is able to prevent accumulation of ox-LDL in arterial walls. This antiatherogenic property of HDL is attributed in part to several enzymes associated with the lipoprotein, including HDL-associated paraoxonase 1 (PON1). In this study we analyzed PON1 arylesterase/paraoxonase activities in relation to serum lipid profile, gender and age in thirty clinically healthy Slovak volunteers. Our results showed that PON1 arylesterase and paraoxonase activities were lower in citrated plasma than in serum by 16.6% and 27.3%, respectively. Among serum lipoproteins, only HDL-cholesterol level showed significant positive correlation with PON1 arylesterase activity (p = 0.042). Likewise, we found a significant relationship between atherogenic index (AI = total cholesterol/HDL-cholesterol) and PON1 arylesterase activity (p = 0.023). No significant correlation could be demonstrated between PON1 paraoxonase activity and serum lipid profile, age or gender. Furthermore, it was found that PON1 paraoxonase/arylesterase activities were higher in women compared with both investigated activities in men, but these differences were not statistically significant. These results confirmed a positive correlation between HDL-cholesterol and PON1 arylesterase activity. Moreover, it was found out that PON1 paraoxonase activity is not influenced either by gender or by age. PON1 arylesterase activity was however affected by gender to a limited extent.     

Paraoxonase activity against nerve gases measured by capillary electrophoresis and characterization of human serum paraoxonase (PON1) polymorphism in the coding region (Q192R)

An analytical method for determining paraoxonase activity against sarin, soman and VX was established. We used capillary electrophoresis to measure directly the hydrolysis products: alkyl methylphosphonates. After enzymatic reaction of human serum paraoxonase (PON1) with nerve gas, substrate was removed with dichloromethane, and alkyl methylphoshphonates were quantified by capillary electrophoresis of reversed osmotic flow using cationic detergent and sorbic acid. This method was applied to the characterization of human serum PON1 polymorphism for nerve gas hydrolytic activity in the coding region (Q192R). PON1-192 and PON1-55 genotypes were determined by their gel electrophoretic fragmentation pattern with restriction enzymes after polymerase chain reaction (PCR) of blood leukocyte genomic DNA. Frequencies of genotypes among 63 members of our institutes with PON1-192 and PON1-55 were 9.5% (¹⁹²QQ), 30.1% (¹⁹²QR) and 44.4% (¹⁹²RR), and 82.5% (⁵⁵LL), 17.5% (⁵⁵LM) and 0% (⁵⁵MM), respectively. ¹⁹²Q and ¹⁹²R enzymes were purified from the respective genotype human plasma, using blue agarose affinity chromatography and diethyl amino ethane (DEAE) anion exchange chromatography. V_max and K_m were measured using Lineweaver-Burk plots for hydrolytic activities against sarin, soman and VX at pH 7.4 and 25 °C. For sarin and soman, the V_max for ¹⁹²Q PON1 were 3.5- and 1.5-fold higher than those for ¹⁹²R PON1; and k_cat/K_m for ¹⁹²Q PON1 were 1.3- and 2.8-fold higher than those for ¹⁹²R PON1. For VX, there was little difference in V_max and k_cat/K_m between ¹⁹²Q and ¹⁹²R PON1, and VX hydrolyzing activity was significantly lower than those for sarin and soman. PON1 hydrolyzed sarin and soman more effectively than paraoxon.     

Polymorphism 192Q/R of the paraoxonase 1 gene in elderly men and long-lived people of the Tatar ethnic group

To study the molecular genetic basis of human aging and longevity, the allele and genotype frequencies of the 192Q/R polymorphism of PON1 were compared for ethnic Tatars of the younger (1–20 years), middle (21–55 years), elderly (56–74 years), senile (75–89 years), and long-lived (90–109 years) age groups (in total, 1116 people). The PON1 alleles were identified using PCR and restriction enzyme analysis. In the total samples, the frequencies of genotypes Q/Q, Q/R, and R/R were 46.15, 44.35, and 9.5%, respectively, and the frequencies of alleles Q and R were 68.32 and 31.68%, respectively. Some age groups significantly differed from each other in allele and genotype frequencies. The frequency of allele R in the senile group (28.46%) was significantly lower than in the younger group (37.42%, P = 0.009). However, the long-lived displayed significantly higher frequencies of allele R (P = 0.005) and genotype R/R (P = 0.01) as compared with the senile group.     

Paraoxonase 1 polymorphisms L55M and Q192R were not risk factors for Parkinson's disease: a HuGE review and meta-analysis

Purpose

The Paraoxonase 1 (PON1) has been studied as a potential candidate gene for Parkinson's disease risk, but direct evidence from genetic association studies remains inconclusive. We performed a meta-analysis pooling data from all relevant studies in order to determine the effects of two PON 1 polymorphisms (L55M and Q192R) on Parkinson's disease.

Methods

We applied a random effects to combine odds ratio (OR) and 95% confidence intervals. Q statistic was used to evaluate the homogeneity, and Egger's test and Funnel plot were used to assess publication bias. In secondary analyses, we examined dominant and recessive models as well.

Results

Concerning the PON1 L55M polymorphism, we identified 9 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR = 1.29, (0.90, 1.84). Concerning the Q192R polymorphism, we identified 7 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR = 1.08(0.81, 1.43). Analysis with dominant and recessive genetic models yielded the same inferences as genotype-based comparisons for both of the two polymorphisms.

Conclusion

The results of this meta-analysis suggested that both PON1 L55M and Q192R were not responsible for PD.     

Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome,but not overweight or obesity

Abstract

Background

The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence.

Aims and methods

This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale.

Results

PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder.

Discussion

PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.     

The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux

Serum paraoxonase (PON1) is a HDL-associated enzyme exhibiting potentially antiatherogenic properties. Here, we examined the common PON1-192R/Q human polymorphism. Despite numerous studies, the effect of this polymorphism on the antiatherogenic potential of PON1 is yet unresolved. Our structural model suggests that amino acid 192 constitutes part of the HDL-anchoring surface and active site of PON1. Based on our findings that PON1 is an interfacially activated lipolactonase that selectively binds HDL carrying apolipoprotein A-I (apoA-I) and is thereby greatly stabilized and catalytically activated, we examined the interaction of the PON1-192 isozymes with reconstituted HDL-apoA-I particles. We found that PON1 position 192 is indeed involved in HDL binding. The PON1-192Q binds HDL with a 3-fold lower affinity than the R isozyme and consequently exhibits significantly reduced stability, lipolactonase activity, and macrophage cholesterol efflux. We also observed the lower affinity and stability of the 192Q versus the 192R isozyme in sera of individuals belonging to the corresponding genotypes. The observed differences in the properties of PON1-192R/Q isozymes provide a basis for further analysis of the contribution of the 192R/Q polymorphism to the susceptibility to atherosclerosis, although other factors, such as the overall levels of PON1, may play a more significant role.     

Complement factor H Y402H polymorphism,plasma concentration and risk of coronary artery disease

Background Inflammation plays an important role in coronary artery disease (CAD). Complement Factor H (CFH) gene has been analyzed in relation to CAD in several studies with conflicting results. The aim of the present study was to investigate the association between the CFH Y402H polymorphism and CAD in Chinese. Methods and results About 336 patients were enrolled, included 166 patients with CAD and 170 controls. The SNP at CFH Y402H was genotyped by ligase detection reaction and plasma levels of CFH were assayed by enzyme-linked immunosorbent assay. Analysis of genotype frequencies did not reveal any significant difference between CAD patients and controls. There were significant differences in the frequencies of C allele and C allele carriers between early-onset CAD and controls. After adjustment of clinical parameters, significant association was identified for CFH Y402H polymorphism, with C allele carriers having a higher risk of early-onset CAD than carriers of TT genotype (odds ratio [OR] 4.66, 95% CI: 1.23–17.62, P = 0.02). There was no difference of plasma CFH levels between CAD group and controls. Conclusions CFH Y402H polymorphism is associated with early-onset CAD in Chinese. Qi Qian and Zhong Chen have contributed equally to this paper.     

TagSNP analyses of the PON gene cluster: effects on PON1 activity, LDL oxidative susceptibility, and vascular disease

Paraoxonase 1 (PON1) activity is consistently predictive of vascular disease, although the genotype at four functional PON1 polymorphisms is not. To address this inconsistency, we investigated the role of all common PON1 genetic variability, as measured by tagging single-nucleotide polymorphisms (tagSNPs), in predicting PON1 activity for phenylacetate hydrolysis, LDL susceptibility to oxidation ex vivo, plasma homocysteine (Hcy) levels, and carotid artery disease (CAAD) status. The biological goal was to establish whether additional common genetic variation beyond consideration of the four known functional SNPs improves prediction of these phenotypes. PON2 and PON3 tagSNPs were secondarily evaluated. Expanded analysis of an additional 26 tagSNPs found evidence of previously undescribed common PON1 polymorphisms that affect PON1 activity independently of the four known functional SNPs. PON1 activity was not significantly correlated with LDL oxidative susceptibility, but genotypes at the PON1(-108) promoter polymorphism and several other PON1 SNPs were. Neither PON1 activity nor PON1 genotype was significantly correlated with plasma Hcy levels. This study revealed previously undetected common functional PON1 polymorphisms that explain 4% of PON1 activity and a high rate of recombination in PON1, but the sum of the common PON1 locus variation does not explain the relationship between PON1 activity and CAAD.     

SOD3 R231G polymorphism associated with coronary artery disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

This study examined the superoxide dismutase 3 (SOD3) R231G polymorphism in relation to the severity of coronary artery disease (CAD) and the risk of myocardial infarction (MI) in 3211 individuals; 94.4% of study participants were homozygous for SOD3 231RR and 5.5% were heterozygous for SOD3 231RG. The odds ratios of the RG and GG genotype (adjusted for age, gender and for conventional cardiovascular risk factors) were 2.02 (95% CI, 1.23–3.33, p=0.005) for the highest vs the lowest Friesinger coronary score and 1.40 (95% CI, 1.02–1.92, p=0.037) for MI, respectively. Further the SOD3 RG and GG genotype was associated with lower alpha-tocopherol levels than the wild type SOD3 RR genotype. It is concluded that the SOD3 231RG and GG genotype is associated with lower alpha-tocopherol levels and the severity of CAD and the risk of MI.     

Analysis of most common mutations R778G, R778L, R778W, I1102T and H1069Q in Indian Wilson disease patients: Correlation between genotype/phenotype/copper ATPase activity

The present study was intented to estimate the frequencies of the most common mutations (R778L, R778W, R778G, I1102T and H1069Q) of ATP7B in Indian Wilson disease (WD) population and to explore the correlation between genotype/phenotype and copper ATPase activity. A total of 33 WD patients and their family members from North West states of India were examined. The H1069Q, R778W and R778L mutations were absent in these WD patients. R778W and I1102T mutations were present in 36% of WD patients. Family analysis for these mutations using PCR-RFLP documented 5 carriers and 2 asymptomatic WD patients. The copper ATPase activity in WD patients was significantly reduced (50%) than that of control individuals. No significant difference was observed in copper stimulated ATPase activity between homozygous (R778W/R778W, I1102T/I1102T) and compound heterozygous (R778W/unknown mutation, I1102T/unknown mutation) WD patients. Serum ceruloplasmin, serum copper levels were significantly lower in homozygous WD patients than that of compound heterozygous. However, no significant difference was observed in liver copper contents between heterozygous and homozygous patients. In conclusion, the data suggest that R778W and I1102T are most common mutations and provide the basis of genetic (PCR-RFLP) diagnostic tool for Indian WD patients as well as in siblings/parents where biochemical parameters are ambiguous.     

Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: A genetic association study and a structural analysis

ATP-binding cassette transporter A1 (ABCA1) has a crucial role in removing intracellular cholesterol and plays a protective role against atherosclerosis. Therefore, genetic polymorphisms in this gene may alter the susceptibility to coronary artery disease (CAD). This study was aimed to examine the association of rs2230806 (c.1051 G > A; p.R219K) variation in the ABCA1 gene with CAD in a case-control design which was followed by a meta-analysis and in silico approach. In the case-control study, 300 subjects including 150 individuals with CAD and 150 healthy controls were recruited. The c.1051 G > A genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, eligible studies were collected from PubMed, Google Scholar, and ScienceDirect databases and pooled odds ratio, heterogeneity, publication bias, and sensitivity analyses were carried. Finally, some bioinformatics tools were employed to assess the impacts of p.R219K variation on ABCA1 protein structure. Our case-control examination showed a statistically significant association between c.1051 G > A genetic polymorphism and CAD risk. In addition, the meta-analysis showed reliable significant associations between c.1051 G > A transition and risk of CAD in the Caucasian population. In silico analysis showed that the p.R219K substitution could alter the secondary structure, hydrophobicity pattern, and Ramachandran plot of ABCA1. These findings elucidate that the c.1051 G > A variation could be a genetic risk factor for CAD and it could be considered as a prognostic and predictive biomarker for susceptible individuals.     

Genetic variation in vitamin D receptor gene (Fok1:rs2228570) is associated with risk of coronary artery disease

Objective: The Fok1 polymorphism (rs2228570) in vitamin D receptor gene appears to be the only polymorphism influencing size of translated protein. Investigations into its association with coronary artery disease (CAD) are sparse.

Methods: Male patients (n?=?98) with verified CAD were recruited alongside age- and sex-matched controls (n?=?55). Genotyping was performed by PCR-RFLP and plasma 25-Hydroxyvitamin D levels were assessed by HPLC-UV.

Results: The C-variant (mutant) was predominantly expressed in patients compared to controls (68.9% versus 55.5%; p?=?0.025). The observed genotypes were not associated with 25-Hydroxyvitamin D levels.

Conclusion: This study presents Fok1 polymorphism as a potential genetic marker for CAD.     

Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease

Objective To determine the incidence of methylene tetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism and plasma homocysteine (Hcy) levels in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD) and to investigate the correlation between hyperhomocysteinemia (HHcy) and the presence of 677C→T polymorphism. Background Elevated plasma Hcy level is an independent risk factor for CAD. A common mutation (677C→T) in the gene coding for MTHFR has been reported to reduce the enzymatic activity and is associated with elevated levels of Hcy, especially in subjects with low folate intake. Methods The study group comprised of 84 patients with CAD and 100 age-and-sex matched controls who had no history or clinical evidence of CAD and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hinf1, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. Results Allele and genotype frequencies in cases and control subjects were compatible with Hardy–Weinberg equilibrium. The frequencies of TT, CT, and CC genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0, 19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease compared to single and double vessel disease (P = 0.002). Multivariate analyses identified HHcy, diabetes mellitus, and hypertension as the independent predictors of CAD. Conclusions HHcy appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings support that homozygous genotype of MTHFR is a genetic risk factor for CAD. A further study with larger sample size including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.     

First survey of the three gene polymorphisms (PON1 Q192R, eNOS E298D and eNOS C-786T) potentially associated with coronary artery spasm in African populations and comparison with worldwide data

Three polymorphisms, Paraoxonase 1 (PON1) Q192R (C/G), endothelial nitric oxide synthase (eNOS) E298D (G/T) and eNOS T‐786C have been suggested to be potentially associated with coronary artery spasm in Japanese patients. Data on worldwide populations are needed to clarify whether these associations could hold true for other populations. However, few data are available especially in Africans, spasm of which has been suggested to be an aetiology of myocardial infarction. Therefore, these polymorphisms were investigated in three Africans, Ovambos (n = 123), Ghanians (n = 118) and Xhosas (n = 96), together with Japanese (n = 96), by using polymerase chain reaction‐restriction fragment length polymorphism analysis. Genotype‐distributions of all these SNPs in African populations were significantly different from those in Caucasians, whereas were similar to those in Japanese population. African populations exhibit relatively higher frequency of spasm‐associated G192 allele in PON1 Q192R being similar to Japanese population, however frequencies of spasm‐associated T298 allele and –C786 allele in SNP eNOS E298D and T‐786C, respectively, were conversely lower in Africans than Caucasians. Although healthy subjects have been recruited in this study, these findings may provide genetic background for elucidation of aetiology of spasm. Copyright © 2011 John Wiley & Sons, Ltd.     

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and −501A > C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674 pg/ml whereas in the hypertensive cohort it was 661 pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (p < 0.05). The controls with the Leu72Leu genotype had less cancer (p < 0.05). In conclusion, high plasma ghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects.