Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Michele P. Marron, Leslie J. Raffel, Henri Jean Garchon, Chaim O. Jacob, Manuel Serrano-Rios, Maria T. Martinez Larrad, Wei Ping Teng, Yongsoo Park, Zhi Xing Zhang, Darlene R. Goldstein, Yi Wen Tao, Genevieve Beaurain, Jean Francois Bach, Hong So Huang, De Fang Luo, Adina Zeidler, Jerome I. Rotter, Mark C.K. Yang, Tamara Modilevsky, Noel K. Maclaren & 1 others Jin-Xiong She

Research output: Contribution to journalArticle

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Abstract

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)(n) microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P= 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10-5), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.

Original languageEnglish (US)
Pages (from-to)1275-1282
Number of pages8
JournalHuman Molecular Genetics
Volume6
Issue number8
DOIs
StatePublished - Aug 1 1997
Externally publishedYes

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Type 1 Diabetes Mellitus
Ethnic Groups
Italy
Alleles
Population
Linkage Disequilibrium
3' Untranslated Regions
Microsatellite Repeats
Spain
Genes
Exons
Datasets

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Marron, M. P., Raffel, L. J., Garchon, H. J., Jacob, C. O., Serrano-Rios, M., Martinez Larrad, M. T., ... She, J-X. (1997). Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Human Molecular Genetics, 6(8), 1275-1282. https://doi.org/10.1093/hmg/6.8.1275

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. / Marron, Michele P.; Raffel, Leslie J.; Garchon, Henri Jean; Jacob, Chaim O.; Serrano-Rios, Manuel; Martinez Larrad, Maria T.; Teng, Wei Ping; Park, Yongsoo; Zhang, Zhi Xing; Goldstein, Darlene R.; Tao, Yi Wen; Beaurain, Genevieve; Bach, Jean Francois; Huang, Hong So; Luo, De Fang; Zeidler, Adina; Rotter, Jerome I.; Yang, Mark C.K.; Modilevsky, Tamara; Maclaren, Noel K.; She, Jin-Xiong.

In: Human Molecular Genetics, Vol. 6, No. 8, 01.08.1997, p. 1275-1282.

Research output: Contribution to journalArticle

Marron, MP, Raffel, LJ, Garchon, HJ, Jacob, CO, Serrano-Rios, M, Martinez Larrad, MT, Teng, WP, Park, Y, Zhang, ZX, Goldstein, DR, Tao, YW, Beaurain, G, Bach, JF, Huang, HS, Luo, DF, Zeidler, A, Rotter, JI, Yang, MCK, Modilevsky, T, Maclaren, NK & She, J-X 1997, 'Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups', Human Molecular Genetics, vol. 6, no. 8, pp. 1275-1282. https://doi.org/10.1093/hmg/6.8.1275
Marron MP, Raffel LJ, Garchon HJ, Jacob CO, Serrano-Rios M, Martinez Larrad MT et al. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Human Molecular Genetics. 1997 Aug 1;6(8):1275-1282. https://doi.org/10.1093/hmg/6.8.1275
Marron, Michele P. ; Raffel, Leslie J. ; Garchon, Henri Jean ; Jacob, Chaim O. ; Serrano-Rios, Manuel ; Martinez Larrad, Maria T. ; Teng, Wei Ping ; Park, Yongsoo ; Zhang, Zhi Xing ; Goldstein, Darlene R. ; Tao, Yi Wen ; Beaurain, Genevieve ; Bach, Jean Francois ; Huang, Hong So ; Luo, De Fang ; Zeidler, Adina ; Rotter, Jerome I. ; Yang, Mark C.K. ; Modilevsky, Tamara ; Maclaren, Noel K. ; She, Jin-Xiong. / Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. In: Human Molecular Genetics. 1997 ; Vol. 6, No. 8. pp. 1275-1282.
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abstract = "Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)(n) microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P= 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10-5), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.",
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AU - Jacob, Chaim O.

AU - Serrano-Rios, Manuel

AU - Martinez Larrad, Maria T.

AU - Teng, Wei Ping

AU - Park, Yongsoo

AU - Zhang, Zhi Xing

AU - Goldstein, Darlene R.

AU - Tao, Yi Wen

AU - Beaurain, Genevieve

AU - Bach, Jean Francois

AU - Huang, Hong So

AU - Luo, De Fang

AU - Zeidler, Adina

AU - Rotter, Jerome I.

AU - Yang, Mark C.K.

AU - Modilevsky, Tamara

AU - Maclaren, Noel K.

AU - She, Jin-Xiong

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N2 - Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)(n) microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P= 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10-5), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.

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