Age of <i>SERPINA1</i> Gene PI Z Mutation: Swedish and Latvian Population Analysis

Lāce, Baiba; Sveger, Tomas; Krams, Alvils; Cernevska, Gunta; Krūmiņa, Astrīda

doi:10.1111/j.1469-1809.2008.00431.x

Cited by 25 publications

(14 citation statements)

References 17 publications

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“…Nevertheless, the findings of this study seem to be in accordance with the reported S and Z frequency distribution worldwide,12–23 and with the hypothesis that both deficiency alleles originate from Caucasians living in Europe at different historical times. It is believed that the Pi*Z mutation has a relatively recent origin in Caucasians living in northern Europe ~2,000 years or 66 generations ago (one generation =30 years),25 and it was spread into the rest of the continent through maritime and inland waterways, via Baltic countries. On the other hand, it has been proposed that the S variant emerged in the Iberian Peninsula 300–450 generations ago (ie, 10–15,000 years ago), and in the Franco-Cantabrian refuge area during the last glacial era, spreading from there by people who later repopulated Europe 26.…”

Section: Discussionmentioning

confidence: 99%

Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

Blanco¹,

Bueno²,

Diego³

et al. 2017

COPD

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The alpha-1 antitrypsin (AAT) haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established. Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects worldwide, based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW) interpolation method, to provide numerical and geographical information of the Pi*SZ distribution worldwide. A total of 262 cohorts from 71 countries were included in the analysis. With the data provided by these cohorts, a total of 1,490,816 Pi*SZ were estimated: 708,792 in Europe; 582,984 in America and Caribbean; 85,925 in Africa; 77,940 in Asia; and 35,176 in Australia and New Zealand. Remarkably, the IDW interpolation maps predicted the Pi*SZ prevalence throughout the entire world even in areas lacking real data. These results may be useful to plan strategies for future research, diagnosis, and management of affected individuals.

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Section: Discussionmentioning

confidence: 99%

Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

Blanco¹,

Bueno²,

Diego³

et al. 2017

COPD

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“…The most common monogenic inborn errors of metabolism associated with liver disease are hereditary hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, and Gilbert's syndrome. These diseases have a particularly high frequency in Northern Europe and Latvia [2][3][4] . Hereditary hemochromatosis is characterized by excessive iron overload and is most commonly caused by HFE gene mutations [2] .…”

Section: Introductionmentioning

confidence: 99%

“…The frequency of the most common HFE mutation, C282Y, is 0.035 in Latvia and 0.026 Lithuania; however, the frequency of hereditary hemochromatosis is lower at 0.013 [5] . Alpha-1 antitrypsin deficiency is caused by the absence of the proteinase inhibitor alpha-1 antitrypsin, and affected patients develop liver disease and emphysema in the third or fourth decade of life [3] . Wilson's disease is a progressive autosomal recessive disorder of copper metabolism.…”

Section: Introductionmentioning

confidence: 99%

Association between inherited monogenic liver disorders and chronic hepatitis C

Piekuse¹,

Kreile²,

Zariņa³

et al. 2014

WJH

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AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS:The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION:Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.

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“…One cluster, including Baltic countries, Poland, and western Russia, has been described, and there are other reports of variants arising from, or being specific to, this region, for example, the Landsteiner Wiener blood (LWb) group, and the PI Z allele in the SERPINA1 gene, among others [14,15] . The first indicator of Baltic genetic influence described was the rs77493670 variant in the ICAM4 gene, also known as the LWb allele [16] .…”

Section: Discussionmentioning

confidence: 99%

A New Baltic Population-Specific Human Genetic Marker in the PMCA4 Gene

Stavusis

Inashkina²,

Lāce³

et al. 2016

Hum Hered

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Objectives: The PMCA gene family consists of 4 genes and at least 21 splice variants; among these, the Ca²⁺ ATPase 4 (PMCA4) gene encodes a plasma membrane protein abundantly expressed in several tissues, including the kidney, heart, and sperm. Knockout of PMCA4 causes infertility due to immotile sperm in mouse models. We therefore investigated variants in this gene for potential association with infertility in groups of Estonian (n = 191) and Latvian (n = 92) men with reduced sperm motility. Methods: All exons, exon-intron boundaries, 5′ and 3′ untranslated regions, and the promoter region of the PMCA4 gene were analysed by direct sequencing for a group of Estonian infertile men. Genotyping of guanine and adenine alleles of rs147729934 was performed, using a custom-designed TaqMan® probe for a group of Latvian infertile men as well as additional groups from Latvia and several groups of people with proven ethnicity from the Baltic region. Results: Although we did not identify any significant associations between variants in the gene and infertility, our results indicated that in all studied Latvian and Estonian groups the adenine allele of the variant rs147729934 was present at a higher frequency than expected. Analysis of additional samples indicated that the adenine allele of rs147729934 likely originated once in the modern-day Baltic or western Russia area, as the frequency of the minor adenine allele observed in this region is remarkably higher than that in the general European population. Conclusions: Our results revealed no significant difference in frequencies of genetic variants in PMCA4 gene between men with normal and those with reduced sperm motility. The adenine allele of the variant rs147729934 is potentially an informative tool for future population studies concerning ancient Baltic and Finno-Ugric history.

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Age of SERPINA1 Gene PI Z Mutation: Swedish and Latvian Population Analysis

Cited by 25 publications

References 17 publications

Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

Association between inherited monogenic liver disorders and chronic hepatitis C

A New Baltic Population-Specific Human Genetic Marker in the PMCA4 Gene

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