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KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects

Saif-Ali R, Muniandy S, Al-Hamodi Z, Lee CS, Ahmed KA, Al-Mekhlafi AM, et al.

Ann Acad Med Singap, 2011 Nov;40(11):488-92.
PMID: 22206064

INTRODUCTION: Type 2 diabetes (T2D) candidate gene: potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) was suggested by conducting a genome wide association study (GWAS) in Japanese population. Association studies have been replicated among East Asian populations; however, the association between this gene and T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of KCNQ1 common variants with type 2 diabetes in Malaysian Malay subjects.
MATERIALS AND METHODS: The KCNQ1 single nucleotide polymorphisms (SNPs): rs2237892, rs2283228, and rs2237895 were genotyped in 234 T2D and 177 normal Malay subjects.
RESULTS: The risk allele of the rs2283228 (A) was strongly associated with T2D (OR = 1.7, P = 0.0006) while the rs2237892 (C) was moderately associated with T2D (OR = 1.45, P = 0.017). The recessive genetic models showed that rs2283228 was strongly associated with T2D (OR = 2.35, P = 0.00005) whereas rs2237892 showed a moderate association with T2D (OR = 1.69, P = 0.01). The haplotype block (TCA), which contained the protective allele, correlated with a protection from T2D (OR = 0.5, P = 0.003). Furthermore, the diplotype (CAA-TCA) that contained the protective haplotype was protected against T2D (OR = 0.46, P = 0.006).
CONCLUSION: The KCNQ1 SNPs, haplotypes and diplotypes are associated with T2D in the Malaysian Malay subjects.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics*
Clinical and genetic analysis of long QT syndrome in two Malay children

Wong AR, Zilfalil BA, Bhuiyan ZA

Med J Malaysia, 2019 08;74(4):341-343.
PMID: 31424047

Long QT syndrome (LQTS) is predominantly a genetic cardiac arrhythmia disorder. We report here our study on long QT syndrome from two children from Kelantan, Malaysia. Clinical and genetic findings of these two unrelated Malay children with LQTS is discussed. We found a Long QT, type 1 causal mutation, p.Ile567Thr in the KCNQ1 gene in the first child. A pathogenic mutation could not be detected in the second child, explaining the heterogeneity of this disease.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics*
Fulltext Recent Progress in Genetics and Epigenetics Research on Diabetic Nephropathy in Malaysia

Abu Seman N, Othman SH

J Diabetes Res, 2023;2023:9053580.
PMID: 37187702 DOI: 10.1155/2023/9053580

Diabetic nephropathy is a multifactorial disease. Gene susceptibility, as well as environmental exposure, plays an important role in disease progression. Malaysia is reported to be among the world's second-fastest-growing rates of kidney failure. Diabetic nephropathy has become the main cause of end-stage renal disease in Malaysia. This article is aimed at reviewing genetic studies conducted among diabetic nephropathy patients in the Malaysian population. This review was conducted by searching PubMed, MEDLINE, and Google Scholar databases to identify all relevant papers published in English from March 2022 to April 2022, using the following keywords: diabetes, type 2 diabetes, diabetic nephropathy, diabetic kidney disease, and Malaysia. The case-control study among diabetic patients with and without diabetic nephropathy showed a significant association with diabetic nephropathy in CNDP1, NOS3, and MnSOD genes. In the ethnic subgroup analysis, significant differences for diabetic nephropathy in terms of diabetes duration (≥10 years) were observed for CCL2 rs3917887, CCR5 rs1799987, ELMO1 rs74130, and IL8 rs4073. The IL8 rs4073 was associated only with the Indians, while the CCR5 rs1799987 was associated with the Chinese. In Malays, SLC12A3 Arg913Gln polymorphism and ICAM1 K469E (A/G) polymorphism were found to be associated with diabetic nephropathy. Studies on gene-environment interactions have suggested significant genetic and environmental factors such as smoking, waist circumference, and sex for eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895, and KCNQ1 rs2283228 with kidney disease. The genetic variants' contributions differed across ethnic groups. Therefore, a study to validate the genetic variants that are found to be associated with different ethnicities in Malaysia may be important in future studies.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics
Fulltext KCNQ1 rs2237892 C→T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta-analysis of 15,736 patients

Li YY, Wang XM, Lu XZ

J Cell Mol Med, 2014 Feb;18(2):274-82.
PMID: 24373634 DOI: 10.1111/jcmm.12185

The KCNQ1 rs2237892 C→T gene polymorphism is reportedly associated with T2DM susceptibility, but various studies show conflicting results. To explore this association in the Asian population, a meta-analysis of 15,736 patients from 10 individual studies was performed. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were evaluated using random-effect or fixed-effect models. A significant relationship between the KCNQ1 rs2237892 C→T gene polymorphism and T2DM was observed in the Asian population under the allelic (OR, 1.350; 95% CI, 1.240-1.480; P KCNQ1 rs2237892 C→T gene polymorphism was found to be significantly associated with increased T2DM risk in the Asian population, except Indian population. The C allele of the KCNQ1 rs2237892 C→T gene polymorphism may confer susceptibility to T2DM.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics*
Fulltext KCNQ1 haplotypes associate with type 2 diabetes in Malaysian Chinese Subjects

Saif-Ali R, Ismail IS, Al-Hamodi Z, Al-Mekhlafi HM, Siang LC, Alabsi AM, et al.

Int J Mol Sci, 2011;12(9):5705-18.
PMID: 22016621 DOI: 10.3390/ijms12095705

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10(-5); OR = 1.9, P = 5.2 × 10(-5); OR = 1.9, P = 7.8 × 10(-5), respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics*
Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore

Koo SH, Ho WF, Lee EJ

Br J Clin Pharmacol, 2006 Mar;61(3):301-8.
PMID: 16487223

To determine the genetic variability of long QT syndrome (LQTS)-associated genes (KCNQ1, HERG, KCNE1 and KCNE2) among three distinct ethnic groups in the Singapore population.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics
Gene-environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case-control study

Ahmad N, Shah SA, Abdul Gafor AH, Abdul Murad NA, Kamaruddin MA, Abd Jalal N, et al.

Diabet Med, 2020 11;37(11):1890-1901.
PMID: 32012348 DOI: 10.1111/dme.14257

AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease.
METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.
RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).
CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.

Matched MeSH terms: KCNQ1 Potassium Channel/genetics*