Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity

Venkatesan Radha, Karani S. Vimaleswaran, Hunsur Narayan S Babu, Nicola Abate, Manisha Chandalia, Pankaj Satija, Scott M. Grundy, Saurabh Ghosh, Partha P. Majumder, Raj Deepa, Sathyanarayana M R Rao, Viswanathan Mohan

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS - South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS - The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS - Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Original languageEnglish (US)
Pages (from-to)1046-1051
Number of pages6
JournalDiabetes Care
Volume29
Issue number5
DOIs
StatePublished - 2006
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Genetic Polymorphisms
Insulin
Glucose Tolerance Test
India
Genotype
Restriction Fragment Length Polymorphisms
Fasting
Phenotype

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects : Evidence for heterogeneity. / Radha, Venkatesan; Vimaleswaran, Karani S.; Babu, Hunsur Narayan S; Abate, Nicola; Chandalia, Manisha; Satija, Pankaj; Grundy, Scott M.; Ghosh, Saurabh; Majumder, Partha P.; Deepa, Raj; Rao, Sathyanarayana M R; Mohan, Viswanathan.

In: Diabetes Care, Vol. 29, No. 5, 2006, p. 1046-1051.

Research output: Contribution to journalArticle

Radha, V, Vimaleswaran, KS, Babu, HNS, Abate, N, Chandalia, M, Satija, P, Grundy, SM, Ghosh, S, Majumder, PP, Deepa, R, Rao, SMR & Mohan, V 2006, 'Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity', Diabetes Care, vol. 29, no. 5, pp. 1046-1051. https://doi.org/10.2337/diacare.2951046
Radha, Venkatesan ; Vimaleswaran, Karani S. ; Babu, Hunsur Narayan S ; Abate, Nicola ; Chandalia, Manisha ; Satija, Pankaj ; Grundy, Scott M. ; Ghosh, Saurabh ; Majumder, Partha P. ; Deepa, Raj ; Rao, Sathyanarayana M R ; Mohan, Viswanathan. / Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects : Evidence for heterogeneity. In: Diabetes Care. 2006 ; Vol. 29, No. 5. pp. 1046-1051.
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abstract = "OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS - South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS - The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9{\%}, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23{\%}) and in India (19 vs. 19.3{\%}). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS - Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.",
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T1 - Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects

T2 - Evidence for heterogeneity

AU - Radha, Venkatesan

AU - Vimaleswaran, Karani S.

AU - Babu, Hunsur Narayan S

AU - Abate, Nicola

AU - Chandalia, Manisha

AU - Satija, Pankaj

AU - Grundy, Scott M.

AU - Ghosh, Saurabh

AU - Majumder, Partha P.

AU - Deepa, Raj

AU - Rao, Sathyanarayana M R

AU - Mohan, Viswanathan

PY - 2006

Y1 - 2006

N2 - OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS - South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS - The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS - Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

AB - OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS - South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS - The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS - Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

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