Prevalence Of Genetic Risk Factors Research Articles

Incidence of Parkinson disease in North America

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Prevalence of genetic risk factors of psoriasis among the population of the Russian Federation

Goal. To assess the prevalence of polymorphisms of genes of the predisposition to psoriasis among the population of the Russian Federation. Materials and methods. The authors examined 546 psoriasis patients and 206 healthy people. The polymorphism of the following genes was assessed: genes encoding proteins of the signaling pathway of the nuclear transcription factor kappa-B - NF-κΒ (NFKBI, TRAF3IP2, TNFAIP3, REL, TYK2, TNIP1, IL-28RA) responsible for congenital immunity; genes participating in the IL-23 signaling pathway responsible for adaptive immunity (IL-23R, IL-12B); genes participating in the presentation of the antigen (ERAP1); genes responsible for skin barrier dysfunction (SERPINB8 ZNF313, ZNF816A). Peripheral blood leucocytes served as the DNA source. Polymorphisms of IL-23R, IL-28RA, SERPINB8, TRAF3IP2, TNFAIP3, REL, ZNF313, IL-12B, TNIP1, ZNF816A, ERAP1 genes were determined by the real-time PCR method; polymorphisms of NFKBI, TYK2 genes were determined by the RFLP assay (Restriction Fragment Length Polymorphism). Results. In psoriasis patients in the Russian Federation, statistically significant differences in the distribution of allele frequencies were determined for IL-23R-G/G, IL-23R-A/A, TRAF3IP2-A/A, TRAF3IP2-G/G, TNFAIP3-A/C, TNFAIP3-A/A, ZNF313-C/C, TYK2-T/T, TYK2-T/G, TNIP1-G/G, TNIP1-A/G, REL-A/A, ERAP1-G/G genotypes.

Prevalence of genetic risk factors related with thrombophilia and hypofibrinolysis in patients with osteonecrosis of the femoral head in Poland

BackgroundThe etiology of osteonecrosis of femoral head (ONFH) has not been fully elucidated. Increased intravascular coagulation and/or hypofibrinolysis have been proposed as pathogenic mechanisms. Previous reports demonstrated significant association between incidence of ONFH and polymorphisms of genes related with thrombophilia especially in Caucasian subjects. The aim of our study was to evaluate the relationship between genetic mutations leading to coagulation disorders and ONFH in Polish patients.MethodsWe have investigated the frequencies of four markers among 68 unrelated individuals with clinically and radiographically documented ONFH and among 100 healthy unrelated blood donors in Eastern part of Poland. The three genes were involved in thrombophilia: factor V Leiden (G1691A), prothrombin (G20210A), Methylenetetrahydrofolate Reductase (MTHFR C677T) and one in hypofibrinolysis: Tissue Plasminogen Activator (PLAT TPA25 I/D). The samples were genotyped with polymerase chain reaction followed by restriction enzyme analysis for the restriction fragment length polymorphisms. The allele and genotype frequencies were analyzed in the relation to ONFH etiology (idiopathic and secondary), gender, age (patients younger or older than 50 years) and the number of affected joints (unilateral or bilateral ONFH).ResultsNo significant difference in allele frequencies between patients and control groups were observed in genes involved in thrombophilia. We have found a statistically significant increased frequency of D allele of PLAT TPA 25 I/D polymorphism between the entire group of patients with ONFH and controls (p=0,026, OR=1,54, CI 0,99-2,4). D allele frequency was also significantly increased in patients with primary ONFH (p=0,009, OR=1,81 CI 1,1-3,01), in males (p= 0,013; OR 1,74; 95% CIs 1,08-2,78), patients older than 50 years (p= 0,018, OR= 2,04; 95% CIs 1,09-3,82) and in cases with bilateral ONFH (p= 0,01; OR= 1,92; 95% CIs 1,13-3,27) (Table 9). The differences in DD homozygous genotype frequency were statistically significant for patients with idiopathic ONFH compared with control group (p=0,023, OR=2,75, CI 0,99-7,9) and in cases of bilateral ONFH (p=0,034; OR 3,12; 95% CIs 1,06-9,18) (Table 10). The frequencies of ID heterozygous genotype were statistically significantly higher in entire group of patients with ONFH (p=0,004 OR 2,71; 95% CIs 1,32-5,57), idiopathic ONFH (p= 0,01; OR 2,91; 95% CIs 1,24-6,87), males (p=0,0007; OR 3,75; 95% CIs 1,67-8,42), patients older than 50 years (p=0,001; OR 6,89; 95% CIs 1,87-25,84) and in cases with bilateral ONFH (p=0,009; OR 3,19; 95% CIs 1,26-8,03).ConclusionThe results suggest that inherited hypofibrinolysis is a risk factor of idiopathic ONFH in Polish population.

Consistency of immigrant suicide rates in Austria with country-of-birth suicide rates: A role for genetic risk factors for suicide?

Multifaceted evidence (family, twin, adoption, molecular genetic, geographic, and surname studies of suicide) suggests genetic risk factors for suicide. The migrant study design is also informative in this context, but underused. In particular, immigrant studies of suicide with a continental European host country are unavailable. The correspondence of suicide prevalence among 22 immigrant groups in Austria (1970–2006) with those of the homelands during the same period was analyzed. Immigrant and homeland suicide rates were significantly positively associated. Controls for age of suicide victim, immigrant group size, national pride, and quality of life in the homelands left the finding essentially unchanged. This correspondence of immigrant and country-of-birth suicide rates is consistent with the assumption of population differences in the prevalence of genetic risk factors for suicide, for which there is emerging evidence.

Consistency of immigrant and country‐of‐birth suicide rates: a meta‐analysis

Multifaceted evidence (family, twin, adoption, molecular genetic, geographic and surname studies of suicide) suggests genetic risk factors for suicide. Migrant studies are also informative in this context, but underused. In particular, a meta-analysis of the associations of immigrant (IMM) and country-of-birth (COB) suicide rates is unavailable. Thirty-three studies, reporting IMM suicide rates for nearly 50 nationalities in seven host countries (Australia, Austria, Canada, England, the Netherlands, Sweden and the USA), were retrieved. Total-population IMM and COB suicide rates were strongly positively associated (combined rank-order correlation across 20 eligible studies: 0.65, 95% CI: 0.56-0.73, P < 10(-9)). The effect generalized across both sexes, host countries and study periods. Following the logic of the migrant study design of genetic epidemiology, the correspondence of IMM and COB suicide rates is consistent with the assumption of population differences in the prevalence of genetic risk factors for suicide.

Superficial venous thrombosis: Prevalence of common genetic risk factors and their role on spreading to deep veins

Introduction Superficial venous thrombosis (SVT) has been considered for a long time a limited clinical condition with a low importance, but this approach has changed in recent years, when several studies demonstrated spreading to deep veins occurring from 7.3 to 44%, with high prevalence of pulmonary embolism. Materials and methods To evaluate the prevalence of genetic risk factors for VTE in patients suffering from SVT on both normal and varicose vein, and to understand their role on spreading to deep veins, we studied 107 patients with SVT, without other risk factors. Ultrasound examination was performed, and the presence of FV Leiden, Prothrombin G20210A mutation, and MTHFR C677T mutation was researched. Results In the patients where SVT occurred in normal veins, the presence of FV Leiden was 26.3% of the non-spreading and 60% of the spreading to deep veins SVT; Prothrombin mutation was found in 7.9% of the former case and in 20% of the latter; MTHFR C677T mutation was found respectively in 23.7% and 40%. In the patients with SVT on varicose veins, the presence of these factors was less evident (6.7%, 4.4% and 6.7% respectively), but their prevalence was considerably higher (35.7%, 7.4% and 21.4% respectively) in SVT spreading to deep veins than in non-spreading. Conclusions Our data demonstrate the high prevalence of these mutations, especially FV Leiden and associations, in patients with SVT on normal veins and their role in the progression to deep vein system.

Torsades de pointes complicating atrioventricular block: Evidence for a genetic predisposition

The prevalence of genetic risk factors has not been systematically evaluated in the setting of complete atriventricular (AV) block complicated by long QT syndrome (LQTS). This study was performed to determine to what extent acquired LQTS in the context of AV block has a genetic substrate. Among 420 recipients of pacemakers implanted over a 3-year period, we identified retrospectively 29 patients with complete AV block and a QT interval >600 ms in duration. A second study group included 22 randomly selected patients who had AV block and a QT interval <600 ms. Normal controls were 100 consecutive individuals without medical history. Genetic studies screening for HERG, KCNQ1 KCNE1, KCNE2, and SCN5A mutations were performed. We identified four mutations on genes encoding potassium channels in five patients with AV block and acquired LQTS. These mutations were not found among patients with AV block and a QT interval <600 ms in duration or in healthy volunteers. Functional expression of three HERG mutations (R328C, R696C, and R1047L) had a dominant negative effect on wild-type I(Kr). One KCNE2 mutation (R77W) identified in a patient treated with flecainide did not alter I(Kr). This study showed that complete AV block complicated by LQTS was associated with HERG mutations in 17% of cases. Further studies are needed to identify factors, genetic or environmental, which may be implicated in bradycardia-related abnormalities of ventricular repolarization.

Prevalence of genetic risk factors for coronary artery disease in Corsica island (France)

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin–Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl A1/A2), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96–18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.

Preeclampsia and its interaction with common variants in thrombophilia genes

Recently, it has been proposed that abnormalities in coagulation and fibrinolysis contribute to the development of preeclampsia by increasing the thrombotic tendency. This hypothesis was tested in women who have had preeclampsia (cases) compared with matched controls. Polymorphisms in the thrombophilia genes [plasminogen activator inhibitor type 1 [PAI-1 -675(4G/5G)], thrombin activatable fibrinolysis inhibitor (TAFI -438G/A and 1040C/T), methylenetetrahydrofolate reductase (MTHFR 677C/T), factor V (FV Leiden R/Q506), prothrombin (FII 20210G/A) and factor XIIIA (FXIIIA V/L34)] were determined in 157 women with preeclampsia and 157 women with uncomplicated pregnancy. The associated risk of preeclampsia was analyzed using logistic regression methods. The frequency distributions of the genotypes of these six polymorphisms in thrombophilia genes were similar in the case and control groups. We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with controls, which makes it unlikely that these polymorphisms are risk factors for preeclampsia.

Risk factors for ovarian cancer: Is there a missing link?

5012 Background: Despite the higher prevalence of BRCA1/2 mutations among Ashkenazi women, ovarian cancer (OvC) incidence among European-American Israeli women is similar to that of Caucasians in the US. Three hypotheses may explain this observation: either Israeli women practice more protective behaviors or Americans are more exposed to risk factors. Alternatively, due to gene-gene or gene-environment interactions, risk factors might affect each population differently. Finally, unidentified risk factors may differ between these populations. Methods: We compared the magnitude and effects of OvC risk factors between Israeli-Jewish and US Pennsylvania women using data from two population-based case-control studies conducted in the 1990s. The Israeli study included 998 cases and 1528 controls individually matched by age and ethnicity. The American group comprised 767 cases frequency matched by age and race to 1367 controls. Both studies used personal interviews to obtain risk factor data. Odds ratios (ORs) adjusted for age, education and race/origin were calculated using logistic regression and compared by Walds Test. Results:Significant differences in the distribution of most study variables were found between the two groups. Israeli women reported more positive family history of OvC, a later age at menarche and menopause, less nulliparity, more livebirths and longer duration of breastfeeding. Oral contraceptive (OC) use and tubal ligation, were significantly more prevalent among US women. Both studies showed consistent results regarding the role of most factors on OvC risk. However, the protective role of OC use and parity was more pronounced in the US (OC use 5+ years vs. never OR= 0.84 and 0.6, p=0.14; livebirth 3+ vs 0 OR= 0.52 & 0.27, p=0.02, Israeli and American groups, respectively). Conclusions: Considering the higher prevalence of genetic risk factors in the Israeli population together with the increased protection for OC use and parity among US women, a modification effect of BRCA1/2 mutations on these factors might exist. Otherwise, these findings might indicate the presence of other unidentified environmental and/or genetic factors that provide increased protection to Israeli women. No significant financial relationships to disclose.

Risk factors for ovarian cancer: Is there a missing link?

5012 Background: Despite the higher prevalence of BRCA1/2 mutations among Ashkenazi women, ovarian cancer (OvC) incidence among European-American Israeli women is similar to that of Caucasians in the US. Three hypotheses may explain this observation: either Israeli women practice more protective behaviors or Americans are more exposed to risk factors. Alternatively, due to gene-gene or gene-environment interactions, risk factors might affect each population differently. Finally, unidentified risk factors may differ between these populations. Methods: We compared the magnitude and effects of OvC risk factors between Israeli-Jewish and US Pennsylvania women using data from two population-based case-control studies conducted in the 1990s. The Israeli study included 998 cases and 1528 controls individually matched by age and ethnicity. The American group comprised 767 cases frequency matched by age and race to 1367 controls. Both studies used personal interviews to obtain risk factor data. Odds ratios (ORs) adjusted for age, education and race/origin were calculated using logistic regression and compared by Walds Test. Results:Significant differences in the distribution of most study variables were found between the two groups. Israeli women reported more positive family history of OvC, a later age at menarche and menopause, less nulliparity, more livebirths and longer duration of breastfeeding. Oral contraceptive (OC) use and tubal ligation, were significantly more prevalent among US women. Both studies showed consistent results regarding the role of most factors on OvC risk. However, the protective role of OC use and parity was more pronounced in the US (OC use 5+ years vs. never OR= 0.84 and 0.6, p=0.14; livebirth 3+ vs 0 OR= 0.52 & 0.27, p=0.02, Israeli and American groups, respectively). Conclusions: Considering the higher prevalence of genetic risk factors in the Israeli population together with the increased protection for OC use and parity among US women, a modification effect of BRCA1/2 mutations on these factors might exist. Otherwise, these findings might indicate the presence of other unidentified environmental and/or genetic factors that provide increased protection to Israeli women. No significant financial relationships to disclose.

Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1000. The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world. Prothrombin G20210A (PT G20210A) gene mutation has been recently identified as a common risk factor in venous thrombosis. Sixty-one patients with VT, differing in age and sex, and 340 healthy subjects were consecutively enrolled into our study to determine the prevalence of PT G20210A in VT and in the healthy population of the southeast of Turkey. The mutation was identified with fluorescence resonance energy transfer (FRET) with the LightCycler polymerase chain reaction. The PT G20210A mutation was found to be 6.5% (4/61) in the VT group and 1.2% (4/340) in the healthy group ( P = 0.021). Three patients with VT had a heterozygous PT G20210A mutation, and the other patient with VT had both Factor V Leiden and PT G20210A mutations. We showed that this method may be used safely for detection of the PT G20210A gene mutation, and the prevalence of PT G20210A mutation is significantly higher in patients with VT than in the healthy population in the southeast of Turkey.

Frequency of Factor V, Prothrombin and Methylenetetrahydrofolate Reductase Gene Variants in Preeclampsia

Background: The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was investigated in a north-eastern Italian population. Methods: Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated. Genotypes were determined by polymerase chain reaction. Results: The frequency of heterozygous carriers of the factor V Leiden was similar between PE women (5.2%) compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A and C677T mutations were similar between PE and control subjects. Conclusions: In this population, we found no difference in the prevalence of genetic risk factors for thrombosis in women with preeclampsia compared with control subjects.

Two common genetic thrombotic risk factors: Factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis

The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world, both in patients with thrombosis and in the general population. Factor V Leiden (FVL) and prothrombin G20210A (PT G20210A) mutations are the most common genetic defects leading to thrombosis. We have previously reported that those two thrombotic risk alleles are frequently found in Turkish children with thrombosis. The aim of the present study was to investigate the frequency of FVL and PT G20210A and their clinical manifestations in adult Turkish patients with thrombosis. Between January 1997 and February 2000, 146 patients with documented thrombosis were investigated in our center for the presence of the FVL and PT G20210A mutations. Forty-five of 146 patients with thrombosis (30.8%) were detected to have FVL mutation. Among those cases with the FVL mutation, seven (4.8%) had homozygote and 38 (26%) had heterozygote mutation. The PT G20210A mutation was detected in 10 of the 146 patients with thrombosis (6.8%). Another six cases (4.1%) had both FVL and PT G20210A mutations. The overall frequency of these two common risk alleles in our adult population with thrombosis was 41.6%. Our findings reveal that FVL and PT G20210A mutations are significant genetic risk factors contributing to the pathophysiology of thrombosis in the Turkish population.

Prevalence of Molecular Risk Factors FV Leiden, FV HR2, FII 20210G&gt;A and MTHFR 677C&gt;T in Different Populations and Ethnic Groups of Germany, Costa Rica and India

The prevalences of the molecular risk factors FVLeiden, FVHis1299Arg (R2), FII 20210G>A and MTHFR 677C>T were studied in blood donors from NE Germany, India (Punjab), San José (Costa Rica), and from two tribes (Chorotegas, Bribri) of Indians and Blacks from Costa Rica. The prevalences of FVL heterozygotes in blood donors from Germany, Costa Rica and India are 6.5, 2 and 1.2% resp. Heterozygosity of R2 allele of FVHR2 was found in 15.5 % in Germany, 13.3% in India. None of the Indians and Blacks of Costa Rica carried FVL, but heterozygotes R1R2 were extremely frequent found in both Indian tribes (44,7% and 50,6%, resp.); homozygosity for R2R2 was 11%. In Blacks the rare R3 polymorphism was found. The FII 20210G>A polymorphism is missing in the Chorotegas Indians and Blacks of Costa Rica and in the population from India. Concerning MTHFR the prevalence of the homozygous mutant genotype is 7.7% in Germany, 5.3% among the Blacks of Costa Rica and 2.7% in India. In the Indian tribes of Costa Rica the prevalence of homozygotes are extremely high: 31.6 % in Chorotegas and 46.7 % in Bribri Indians. The prevalence of genetic risk factors in various populations and ethnic groups is discussed.

Prevalence of Molecular Risk Factors FV Leiden, FV HR2, FII 20210G&gt;A and MTHFR 677C&gt;T in Different Populations and Ethnic Groups of Germany, Costa Rica and India

The prevalences of the molecular risk fac- tors FVLeiden, FVHis1299Arg (R2), FII 20210G>A and MTHFR 677C>T were studied in blood donors from NE Germany, India (Punjab), San Jose ( Costa Rica), and from two tribes (Chorotegas, Bribri) of Indians and Blacks from Costa Rica. The prevalences of FVL heterozygotes in blood donors from Germany, Costa Rica and India are 6.5, 2 and 1.2% resp. Heterozygosity of R2 allele of FVHR2 was found in 15.5 % in Germany, 13.3% in India. None of the Indians and Blacks of Costa Rica carried FVL, but heterozygotes R1R2 were extremely frequent found in both Indian tribes (44,7% and 50,6%,resp.); homozygosity for R2R2 was 11%. In Blacks the rare R3 polymorphism was found. The FII 20210G>A polymorphism is missing in the Chorotegas Indians and Blacks of Costa Rica and in the population from India. Concerning MTHFR the prevalence of the ho- mozygous mutant genotype is 7.7% in Germany, 5.3% among the Blacks of Costa Rica and 2.7% in India. In the Indian tribes of Costa Rica the prevalence of homozygotes are extremely high: 31.6 % in Chorotegas and 46.7 % in Bribri Indians. The prevalence of genetic risk factors in various populations and ethnic groups is discussed.

Preeclampsia and genetic risk factors for thrombosis: A case-control study

Objective: Recently, it has been proposed that hereditary coagulation abnormalities leading to an increased venous thrombosis risk may play a role in the development of preeclampsia. We tested this hypothesis in women who have had preeclampsia compared with matched control subjects. Study Design: We conducted a case-control study of 163 women with preeclampsia during 1991-1996. Control subjects were matched for age and delivery date. Patients and control subjects were tested for the presence of factor V Leiden, prothrombin 20210A allele, protein C, protein S, and antithrombin deficiency. Logistic regression methods were used for data analysis. Results: The prevalence of these genetic risk factors was similar in the patient group (12.9%) and the control group (12.9%; odds ratio, 1.0; 95% confidence interval, 0.5-3.9). Unexpectedly, we found a high prevalence of factor V Leiden in the control group (9.2%). Conclusion: We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with control subjects. (Am J Obstet Gynecol 1999;181:975-80.)

Apolipoprotein E and B polymorphisms - longevity factors assessed in nonagenarians

To test if the prevalence of genetic risk factors for coronary heart disease (CHD) is low in individuals who have reached an extremely old age, the allele frequencies of apolipoprotein E (apo E) and B (apo B) polymorphisms and plasma lipoprotein(a) levels were investigated in nonagenarians and in younger control groups. The frequency of the ϵ4 alle of apo significantly lower in the nonagenarians than in the middle-aged and young adults ( P < 0.05). Also, the frequency of EcoRl allele R- of apo B was low in the nonagenarians, whereas the allele frequency for the Xbal polymorphism of apo B and plasma lipoprotein(a) concentrations did not differ between the nonagenarians and the younger groups. These findings strongly suggest that the presence of these potential genetic risk factors for CHD, namely the e4 allele of apo E and the R- allele of apo B, decreases the probability of an individual reaching an extremely old age.