Genetic variants in Transient Receptor Potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans

Farook Thameem, Sobha Puppala, Nedal H. Arar, John Blangero, Ravindranath Duggirala, Hanna E. Abboud

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Evidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR). Methods: To identify the sequence variants, the exons and 2. kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR. Results: Sequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P=0.039). Conclusion: The present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.

Original languageEnglish (US)
Pages (from-to)2058-2062
Number of pages5
JournalClinica Chimica Acta
Volume412
Issue number23-24
DOIs
StatePublished - Nov 20 2011

Fingerprint

Transient Receptor Potential Channels
Albuminuria
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Albumins
Creatinine
Medical problems
Genetic Promoter Regions
Association reactions
Genes
Blood Pressure
Terminator Codon
Blood pressure
Chromosomes
Introns
Type 2 Diabetes Mellitus
Antihypertensive Agents
Sequence Analysis
Exons

Keywords

  • Albumin to creatinine ration
  • Association analysis
  • Mexican americans
  • Polymorphisms
  • TRPM1
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Genetic variants in Transient Receptor Potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans. / Thameem, Farook; Puppala, Sobha; Arar, Nedal H.; Blangero, John; Duggirala, Ravindranath; Abboud, Hanna E.

In: Clinica Chimica Acta, Vol. 412, No. 23-24, 20.11.2011, p. 2058-2062.

Research output: Contribution to journalArticle

Thameem, Farook ; Puppala, Sobha ; Arar, Nedal H. ; Blangero, John ; Duggirala, Ravindranath ; Abboud, Hanna E. / Genetic variants in Transient Receptor Potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans. In: Clinica Chimica Acta. 2011 ; Vol. 412, No. 23-24. pp. 2058-2062.
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abstract = "Background: Evidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR). Methods: To identify the sequence variants, the exons and 2. kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR. Results: Sequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P=0.039). Conclusion: The present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.",
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T1 - Genetic variants in Transient Receptor Potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans

AU - Thameem, Farook

AU - Puppala, Sobha

AU - Arar, Nedal H.

AU - Blangero, John

AU - Duggirala, Ravindranath

AU - Abboud, Hanna E.

PY - 2011/11/20

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N2 - Background: Evidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR). Methods: To identify the sequence variants, the exons and 2. kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR. Results: Sequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P=0.039). Conclusion: The present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.

AB - Background: Evidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR). Methods: To identify the sequence variants, the exons and 2. kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR. Results: Sequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P=0.039). Conclusion: The present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.

KW - Albumin to creatinine ration

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KW - Mexican americans

KW - Polymorphisms

KW - TRPM1

KW - Type 2 diabetes

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