Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris

Miquel, Juan Francisco; Covarrubias, Carmen; Villaroel, Luis; Mingrone, Geltrude; Greco, Aldo V.; Puglielli, Luigi; Carvallo, Pilar; Marshall, Guillermo; Pino, Guido del; Nervi, Flavio

doi:10.1016/s0016-5085(98)70266-5

Cited by 211 publications

(210 citation statements)

References 56 publications

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“…A prevalence of cholelithiasis of 25% detected in our study among chronic SCI male patients, surpasses extensively the prevalence among the general male population of our country, reported by Miquel 9 and which is of 13,1% for Hispanics and of 12.6% for Mapuches. In view of this, we cannot assume that the prevalence we found among our SCI patients is due to the higher prevalence of cholelithiasis reported for the general Chilean population.…”

Section: Discussioncontrasting

confidence: 68%

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Gallstones in spinal cord injury (SCI): a late medical complication?

Rotter

Larraín

2003

Spinal Cord

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Study design: Prospective controlled study. Objectives: To assess the prevalence of cholelithiasis among chronic spinal spinal cord injured (SCI) male patients of the ACHS (AsociacioÂ n Chilena de Seguridad). To evaluate statistically the prevalence of cholelithiasis among SCI patients compared to a control group and to the general male Chilean population. To assess the correlation between cholelithiasis in chronic SCI patients and usual risk factors such as age, obesity and diabetes mellitus. To assess the association of cholelithiasis in chronic SCI patients and the duration of the spinal cord injury. Setting: Rehabilitation Service at the Hospital del Trabajador, in Santiago, Chile. Methods: One hundred SCI patients followed up at the Hospital del Trabajador on a regular basis were included in the study; one group consisted of 76 subjects rated ASIA A or B and the other group consisted of 24 subjects rated ASIA C and D. They were all male, older than 20 years old (average age: 41,9 and 42,6 respectively), and su ered from a spinal cord injury greater than one year of evolution. The control group (CG) consisted of 100 male volunteers, without both SCI and history of biliary disease, aged 40.3 years old in average. All three groups underwent ultrasonographic imaging evaluation of the gallbladder and the biliary tract between 1998 and 2000. Results: The prevalence of cholelithiasis among the groups was the following: 25% in the SCI patients ASIA A and B (19/76), 25% in the SCI patients ASIA C and D (6/24) and 9% (1/100) in the CG. The statistical analysis showed a value of P=0.0037, thus establishing a signi®cant association between cholelithiasis and SCI, both complete and incomplete. The di erence was not statistically signi®cant when correlating the presence of cholelithiasis with the neurological level of the injury ± above and below T10 (24,1 and 25%, respectively) ± with the duration of the SCI, with age, obesity and diabetes mellitus. Conclusions: SCI represents a major risk factor for the development of cholelithiasis, and it should be considered a late, secondary complication of a spinal cord injury. Sponsorship: The present work is sponsored by the FundacioÂ n CientõÂ ®ca y TecnoloÂ gica of the ACHS, grant No 2899.

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Section: Discussioncontrasting

confidence: 68%

“…The reasons for the high prevalence of cholelithiasis in Chile remain unknown, and at present, ethnic and racial factors appear to be the most relevant. 9 Additionally, there is also a greater prevalence of cancer of the biliary tract among the Chilean population. 10,11 …”

Section: Introductionmentioning

confidence: 99%

Gallstones in spinal cord injury (SCI): a late medical complication?

Rotter

Larraín

2003

Spinal Cord

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“…Analyses of the p.(Ala359Asp) variant frequency in the Chilean population and theoretical incidence rate of NPDB in Chile The samples analyzed were Hispanics from a mixed Chilean/Spaniard origin and are representative of at least 70% of the Chilean population, from the center and south of Chile and were studied before by Miquel et al 20 Analysis of 1921 DNA samples from unaffected individuals by the Taqman allelic discrimination assay yielded an 88.0% call rate of informative DNA samples (1691). Sixteen out of 1691 (0.95%) samples were heterozygous for the p.(Ala359Asp) variant.…”

Section: Resultsmentioning

confidence: 99%

Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann–Pick disease type B

Acuña

Martínez

Moraga³

et al. 2015

Eur J Hum Genet

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Niemann-Pick disease type B (NPDB) is a rare, inherited lysosomal storage disorder that occurs due to variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene and the resultant deficiency of acid sphingomyelinase (ASM) activity. While numerous variants causing NPDB have been described, only a small number have been studied in any detail. Herein, we describe the frequency of the p.(Ala359Asp) variant in the healthy Chilean population, and determine the haplotype background of homozygous patients to establish if this variant originated from a common founder. Genomic DNA samples from 1691 healthy individuals were analyzed for the p.(Ala359Asp) variant. The frequency of p.(Ala359Asp) was found to be 1/105.7, predicting a disease incidence of 1/44 960 in Chile, higher than the incidence estimated by the number of confirmed NPDB cases. We also describe the clinical characteristics of 13 patients homozygous for p.(Ala359Asp) and all of them had moderate to severe NPDB disease. In addition, a conserved haplotype and shared 280 Kb region around the SMPD1 gene was observed in the patients analyzed, indicating that the variant originated from a common ancestor. The haplotype frequency and mitochondrial DNA analysis suggest an Amerindian origin for the variant. To assess the effect of the p.(Ala359Asp) variant, we transfected cells with the ASM-p.(Ala359Asp) cDNA and the activity was only 4.2% compared with the wild-type cDNA, definitively demonstrating the causative effect of the variant on ASM function. Information on common variants such as p. (Ala359Asp) is essential to guide the successful implementation for future therapies and benefit to patients.

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“…As reviewed recently, 7,8 the results of epidemiological studies 9 and familial clustering of gallstones indicate that genetic factors influence the risk of gallstone formation. In most patients gallstones are likely to develop as a result of lithogenic polymorphisms in several genes and their interactions with multiple environmental factors, rendering gallstones a complex genetic disease.…”

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confidence: 99%

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

et al. 2007

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Genomewide scans of inbred strains of mice have linked the genes encoding the hepatocanalicular cholesterol transporter ABCG5/G8 to gallstone formation. Five nonsynonymous coding single-nucleotide polymorphisms (SNPs) in the orthologous human genes are associated with differences in serum cholesterol and plant sterol levels. We now tested these ABCG5/G8 SNPs for linkage and association with gallstone susceptibility in humans. Prospectively, we collected data from 178 white individuals with gallbladder stones or history of cholecystectomy in 84 families and from 70 stone-free controls, as confirmed by abdominal ultrasound. We performed nonparametric linkage (NPL) analysis of affected sib pairs (ASPs) and association tests of cases and controls. In ASPs, gallstones were strongly linked to the D19H variant of the ABCG8 gene (NPL score ‫؍‬ 7.1; P ‫؍‬ 4.6 ؋ 10 ؊13 ). The risk of gallstones in carriers of the 19H allele was significantly increased in randomly selected cases from the ASP cohort compared to the stone-free controls (OR ‫؍‬ 3.018; P ‫؍‬ 0.017). Consistent with the mouse model, heterozygosity for the lithogenic ABCG8 allele was associated with gallstones in humans; 21.4% of gallstone patients carried the heterozygous D19H genotype, compared with 8.6% of controls (OR ‫؍‬ 2.954; P ‫؍‬ 0.026). Conclusion: The linkage and association studies identified the cholesterol transporter ABCG5/G8 as a genetic determinant of gallstone formation, or LITH gene, in humans. The function of this transporter and the results of the genetic study taken together indicate that in gallstone-susceptible carriers of the ABCG8 19H allele, cholesterol cholelithiasis is secondary to increased hepatobiliary cholesterol secretion. (HEPATOLOGY 2007;46:793-801.)

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Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris

Cited by 211 publications

References 56 publications

Gallstones in spinal cord injury (SCI): a late medical complication?

Gallstones in spinal cord injury (SCI): a late medical complication?

Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann–Pick disease type B

Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol

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