14 results on '"rs3798220"'
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2. LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels
- Author
-
Andreja Rehberger Likozar, Aleš Blinc, Katarina Trebušak Podkrajšek, and Miran Šebeštjen
- Subjects
coronary artery disease ,lipoprotein(a) ,rs10455872 ,rs3798220 ,KIV-2 repeats ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties.
- Published
- 2021
- Full Text
- View/download PDF
3. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus.
- Author
-
Singh, Sunny S., Rashid, Mardin, Lieverse, Aloysius G., Kronenberg, Florian, Lamina, Claudia, Mulder, Monique T., de Rijke, Yolanda B., Sijbrands, Eric J. G., and van Hoek, Mandy
- Abstract
Aims/hypothesis: Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods: Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA
1c and smoking). Results: No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation: Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
4. Lipoprotein(a) Gene Polymorphism Increases a Risk Factor for Aortic Valve Calcification
- Author
-
Ugur Ozkan, Fatih Ozcelik, Mustafa Yildiz, and Metin Budak
- Subjects
Lp(a) level ,rs10455872 ,rs3798220 ,calcific aortic valve stenosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Calcific aortic valve disease (CAVD) is a multifactorial condition. Both environmental and genetic factors play an important role in its etiology. CAVD exhibits a broad spectrum, varying from mild valve thickening to severe valve calcification and stenosis. Progression of the disease consists of chronic inflammation, lipoprotein deposition, and active leaflet calcification. It is a process similar to coronary artery disease. In this study, we investigated Lp(a) levels and gene polymorphisms associated with calcific aortic stenosis from blood samples after echocardiography in the evaluation of 75 patients diagnosed with CAVD and 77 controls. Blood tests were run in our laboratory to rule out certain risk factors before echocardiography examination. A significant association among smoking, elevated LDL level and creatinine, low albumin levels, Lp(a) level, rs10455872, and rs3798220 polymorphisms may be considered genetic risk factors for the development of calcific aortic stenosis.
- Published
- 2019
- Full Text
- View/download PDF
5. LPA genotypes and haplotypes are associated with lipoprotein(a) levels but not arterial wall properties in stable post-coronary event patients with very high lipoprotein(a) levels
- Author
-
Ales Blinc, Katarina Trebusak Podkrajsek, Andreja Rehberger Likozar, and Miran Sebestjen
- Subjects
haplotypes ,rs3798220 ,Article ,KIV-2 repeats ,bolezen koronarnih arterij ,lipoprotein(a) ,RC666-701 ,haplotipi ,LPA genotypes ,Diseases of the circulatory (Cardiovascular) system ,Pharmacology (medical) ,rs10455872 ,General Pharmacology, Toxicology and Pharmaceutics ,coronary artery disease ,genotipi LPA ,udc:616.1 - Abstract
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties.
- Published
- 2022
6. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus
- Author
-
Mandy van Hoek, Yolanda B. de Rijke, M. Rashid, Florian Kronenberg, Sunny S Singh, Monique T. Mulder, Aloysius G Lieverse, Eric J.G. Sijbrands, Claudia Lamina, Internal Medicine, and Clinical Chemistry
- Subjects
Male ,medicine.medical_specialty ,Microvascular complications ,Endocrinology, Diabetes and Metabolism ,Population ,SNP ,Type 2 diabetes ,rs3798220 ,Gastroenterology ,Polymorphism, Single Nucleotide ,Article ,Nephropathy ,Lp(a) ,SDG 3 - Good Health and Well-being ,Risk Factors ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,rs10455872 ,Prospective Studies ,Risk factor ,education ,Prospective cohort study ,Retinopathy ,Macrovascular disease ,Aged ,education.field_of_study ,biology ,business.industry ,Type 2 Diabetes Mellitus ,Lipoprotein(a) ,Middle Aged ,medicine.disease ,Spline ,Neuropathy ,LPA ,Diabetes Mellitus, Type 2 ,biology.protein ,Female ,business - Abstract
Aims/hypothesis Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications.
- Published
- 2020
7. Genotyping of Lipoprotein(a) Gene Variants in Coronary Artery Disease in Indian Population
- Author
-
Charanjeet Kaur, Anu Ri, Prabhash Bhavsar, and Jagdish Prasad
- Subjects
Genetics ,biology ,business.industry ,Indian population ,rs1321196 ,Allele-specific PCR ,General Medicine ,Lipoprotein(a) ,Cardiovascular genetics ,rs3798220 ,medicine.disease ,Coronary artery disease ,biology.protein ,Medicine ,LPA aspirin genotype ,LPA gene polymorphism ,business ,Variants of PCR ,Molecular cardiology ,Gene ,Genotyping ,rs9364564 - Abstract
India is undergoing an epidemiological transition and an alarming rise in the prevalence of coronary artery disease (CAD). The etiopathology of the disease is evolving to a more complex setting with the discovery of novel risk factors. In the quest for non-traditional risk factors, we found that Lipoprotein(a) gene and its product are unique and pertinent to the Indian population. To unravel the genetic blueprint of the variations within theLPAgene in Indians, we studied novel exonic and intronic SNPs in 60 patients with angiographically proven CAD and matched them with healthy volunteers. From the study, we observed that in our patients,LPAaspirin genotype rs3798220 did not cause variation in Lp(a) levels in either of the two groups which is a novel finding as it is at odds with most published studies from other populations, on this variant. The polymorphic allele of SNP rs1321196 increased serum Lp(a) levels but the presence of the variant was however not limited to the patient population. The SNP rs9364564 did not influence Lp(a) levels in either of the two groups of the study. The study is unique as it bears witness to the novelty of the genotype background in Indian patients with CAD.
- Published
- 2021
8. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus
- Author
-
Singh, S.S. (Sunny S.), Rashid, M. (Mardin), Lieverse, A.G. (Aloysius), Kronenberg, F. (Florian), Lamina, C. (Claudia), Mulder, M.T. (Monique), de Rijke, Y.B. (Yolanda B.), Sijbrands, E.J.G. (Eric), Hoek, M. (Mandy) van, Singh, S.S. (Sunny S.), Rashid, M. (Mardin), Lieverse, A.G. (Aloysius), Kronenberg, F. (Florian), Lamina, C. (Claudia), Mulder, M.T. (Monique), de Rijke, Y.B. (Yolanda B.), Sijbrands, E.J.G. (Eric), and Hoek, M. (Mandy) van
- Abstract
Aims/hypothesis: Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods: Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results: No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation: Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the develo
- Published
- 2020
- Full Text
- View/download PDF
9. LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography.
- Author
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Santos, Paulo C. J. L., Bueno, Carolina T., Lemos, Pedro A., Krieger, José E., and Pereira, Alexandre C.
- Subjects
- *
CORONARY angiography , *GENETIC polymorphisms , *CARDIAC imaging , *POPULATION genetics - Abstract
Background Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95%CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95%CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels.
- Author
-
Rehberger Likozar A, Blinc A, Trebušak Podkrajšek K, and Šebeštjen M
- Abstract
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) ( LPA ) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = -0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties.
- Published
- 2021
- Full Text
- View/download PDF
11. LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography
- Author
-
Alexandre C. Pereira, José Eduardo Krieger, Paulo Cjl Santos, Pedro A. Lemos, and Carolina Tosin Bueno
- Subjects
Coronary angiography ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Clinical nutrition ,Coronary Artery Disease ,rs3798220 ,Coronary Angiography ,Coronary artery disease ,Endocrinology ,Internal medicine ,medicine ,Odds Ratio ,Humans ,Coronary lesions ,Genetic Predisposition to Disease ,rs10455872 ,Allele ,Alleles ,Aged ,Biochemistry, medical ,Polymorphism, Genetic ,biology ,business.industry ,Research ,Biochemistry (medical) ,Lipoprotein(a) ,Odds ratio ,Middle Aged ,medicine.disease ,biology.protein ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Female ,LPA gene ,business ,Brazil ,Lipidology - Abstract
Background Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95% CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95% CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association.
- Published
- 2014
12. Lipoprotein(a) Gene Polymorphism Increases a Risk Factor for Aortic Valve Calcification.
- Author
-
Ozkan U, Ozcelik F, Yildiz M, and Budak M
- Abstract
Calcific aortic valve disease (CAVD) is a multifactorial condition. Both environmental andgenetic factors play an important role in its etiology. CAVD exhibits a broad spectrum, varying frommild valve thickening to severe valve calcification and stenosis. Progression of the disease consistsof chronic inflammation, lipoprotein deposition, and active leaflet calcification. It is a process similarto coronary artery disease. In this study, we investigated Lp(a) levels and gene polymorphismsassociated with calcific aortic stenosis from blood samples after echocardiography in the evaluationof 75 patients diagnosed with CAVD and 77 controls. Blood tests were run in our laboratory to ruleout certain risk factors before echocardiography examination. A significant association amongsmoking, elevated LDL level and creatinine, low albumin levels, Lp(a) level, rs10455872, andrs3798220 polymorphisms may be considered genetic risk factors for the development of calcificaortic stenosis., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
- Full Text
- View/download PDF
13. Sequence variation in the human LPA gene
- Author
-
Noureen, Asma and Noureen, Asma
- Abstract
LPA is the major locus controlling Lp(a) plasma levels which vary extensively within and across populations and are associated with coronary heart disease. Identified causal genetic polymorphisms, including the KIV-2 CNV and other sequence variants, explain only a fraction of the variation in Lp(a) levels attributable to the LPA locus. Therefore additional sequence variation in LPA is expected to explain more of the observed variation in Lp(a) levels. One region of LPA not yet fully screened for such sequence variants is the KIV-2 CNV. Some variants in this region have been reported by the large re-sequencing projects but for those variants any data on the Lp(a) levels and the KIV-2 CNV size are missing. In one projects of this thesis, coding regions of the KIV 2 CNV were screened in individuals from six different populations (Gabonese Bantu, South African Bantu, Khoi San, Egyptians, Hong Kong Chinese and Austrians). LPA alleles of each individual were separated by PFGE and used for batchwise amplification of PCR fragments specific for the two exons of KIV-2. Despite a restricted sample size (in total 90 alleles) and limited sensitivity of the screening method used, several synonymous and non-synonymous variants as well as two previously unreported splice site variants were identified. Most of these variants were detected in African alleles. Among the variants found, an African specific acceptor splice site variant (K422 6T>G) associated with small KIV-2 CNV size was present in all African populations at high population frequencies (10% to 40%). This variant appears to be associated with low Lp(a) levels than expected considering the KIV-2 CNV size of the alleles carrying it. In contrast to the frequent African specific acceptor splice site variant, a rare donor splice site variant (K421 +1G>A) was found which was shared among Africans and Europeans and associated with non-detectable Lp(a). In Asians, only the synonymous variants that define the KIV 2 type B and typ, LPA is the major locus controlling Lp(a) plasma levels which vary extensively within and across populations and are associated with coronary heart disease. Identified causal genetic polymorphisms, including the KIV-2 CNV and other sequence variants, explain only a fraction of the variation in Lp(a) levels attributable to the LPA locus. Therefore additional sequence variation in LPA is expected to explain more of the observed variation in Lp(a) levels. One region of LPA not yet fully screened for such sequence variants is the KIV-2 CNV. Some variants in this region have been reported by the large re-sequencing projects but for those variants any data on the Lp(a) levels and the KIV-2 CNV size are missing. In one projects of this thesis, coding regions of the KIV 2 CNV were screened in individuals from six different populations (Gabonese Bantu, South African Bantu, Khoi San, Egyptians, Hong Kong Chinese and Austrians). LPA alleles of each individual were separated by PFGE and used for batchwise amplification of PCR fragments specific for the two exons of KIV-2. Despite a restricted sample size (in total 90 alleles) and limited sensitivity of the screening method used, several synonymous and non-synonymous variants as well as two previously unreported splice site variants were identified. Most of these variants were detected in African alleles. Among the variants found, an African specific acceptor splice site variant (K422 6T>G) associated with small KIV-2 CNV size was present in all African populations at high population frequencies (10% to 40%). This variant appears to be associated with low Lp(a) levels than expected considering the KIV-2 CNV size of the alleles carrying it. In contrast to the frequent African specific acceptor splice site variant, a rare donor splice site variant (K421 +1G>A) was found, by Asma Noureen, Kumulative Dissertation aus zwei Artikeln, Dissertation Medical University of Innsbruck 2015
14. Sequence variation in the human LPA gene
- Author
-
Noureen, Asma and Noureen, Asma
- Abstract
LPA is the major locus controlling Lp(a) plasma levels which vary extensively within and across populations and are associated with coronary heart disease. Identified causal genetic polymorphisms, including the KIV-2 CNV and other sequence variants, explain only a fraction of the variation in Lp(a) levels attributable to the LPA locus. Therefore additional sequence variation in LPA is expected to explain more of the observed variation in Lp(a) levels. One region of LPA not yet fully screened for such sequence variants is the KIV-2 CNV. Some variants in this region have been reported by the large re-sequencing projects but for those variants any data on the Lp(a) levels and the KIV-2 CNV size are missing. In one projects of this thesis, coding regions of the KIV 2 CNV were screened in individuals from six different populations (Gabonese Bantu, South African Bantu, Khoi San, Egyptians, Hong Kong Chinese and Austrians). LPA alleles of each individual were separated by PFGE and used for batchwise amplification of PCR fragments specific for the two exons of KIV-2. Despite a restricted sample size (in total 90 alleles) and limited sensitivity of the screening method used, several synonymous and non-synonymous variants as well as two previously unreported splice site variants were identified. Most of these variants were detected in African alleles. Among the variants found, an African specific acceptor splice site variant (K422 6T>G) associated with small KIV-2 CNV size was present in all African populations at high population frequencies (10% to 40%). This variant appears to be associated with low Lp(a) levels than expected considering the KIV-2 CNV size of the alleles carrying it. In contrast to the frequent African specific acceptor splice site variant, a rare donor splice site variant (K421 +1G>A) was found which was shared among Africans and Europeans and associated with non-detectable Lp(a). In Asians, only the synonymous variants that define the KIV 2 type B and typ, LPA is the major locus controlling Lp(a) plasma levels which vary extensively within and across populations and are associated with coronary heart disease. Identified causal genetic polymorphisms, including the KIV-2 CNV and other sequence variants, explain only a fraction of the variation in Lp(a) levels attributable to the LPA locus. Therefore additional sequence variation in LPA is expected to explain more of the observed variation in Lp(a) levels. One region of LPA not yet fully screened for such sequence variants is the KIV-2 CNV. Some variants in this region have been reported by the large re-sequencing projects but for those variants any data on the Lp(a) levels and the KIV-2 CNV size are missing. In one projects of this thesis, coding regions of the KIV 2 CNV were screened in individuals from six different populations (Gabonese Bantu, South African Bantu, Khoi San, Egyptians, Hong Kong Chinese and Austrians). LPA alleles of each individual were separated by PFGE and used for batchwise amplification of PCR fragments specific for the two exons of KIV-2. Despite a restricted sample size (in total 90 alleles) and limited sensitivity of the screening method used, several synonymous and non-synonymous variants as well as two previously unreported splice site variants were identified. Most of these variants were detected in African alleles. Among the variants found, an African specific acceptor splice site variant (K422 6T>G) associated with small KIV-2 CNV size was present in all African populations at high population frequencies (10% to 40%). This variant appears to be associated with low Lp(a) levels than expected considering the KIV-2 CNV size of the alleles carrying it. In contrast to the frequent African specific acceptor splice site variant, a rare donor splice site variant (K421 +1G>A) was found, by Asma Noureen, Kumulative Dissertation aus zwei Artikeln, Dissertation Medical University of Innsbruck 2015
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