Lack of association of the insulin gene region with Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects

Matsumoto, Chiaki; Awata, Takuya; Iwamoto, Yasuhiko; Kuzuya, Tsunehiko; Saito, Toshikazu; Kanazawa, Yasunori

doi:10.1007/s001250050095

Cited by 13 publications

(11 citation statements)

References 22 publications

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“…This could reflect disease heterogeneity. The very high frequency of INS + / + in Japanese is in agreement with studies applying the 5'VNTR polymorphism to assess the INS genotype [18][19][20][21][22]. None of these previous studies have shown any contribution of the INS region to IDDM susceptibility among Japanese subjects.…”

Section: Discussionsupporting

confidence: 74%

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IDDM susceptibility associated with polymorphisms in the insulin gene region A study of blacks, Caucasians and orientals

Undlien¹,

Hamaguchi

Kimura

et al. 1994

Diabetologia

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SummaryPrevious studies have suggested an association between polymorphisms in the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Most of the studies so far have been performed in Caucasoid populations. We have investigated 418 random IDDM patients and 422 healthy control subjects from three different ethnic groups; Tanzanian blacks, Norwegian Caucasians and Japanese orientals. Our data suggest that polymorphisms in the insulin gene region confer susceptibility to IDDM in Caucasians, and that a similar tendency though not statistically significant is observed among Tanzanian blacks, while no significant contribution is seen among Japanese orientals. We further demonstrate that the disease-associated genotype INS +/+ confers susceptibility independently of HLA class II alleles associated with IDDM. Compared to the contribution of particular HLA-DQ alleles in IDDM susceptibility, the additional risk conferred by the instdin gene region polymorphism is, however, small. Genotyping of the insulin gene region will therefore most probably not be a useful tool in the prediction of IDDM. [Diabetologia (1994)

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Section: Discussionsupporting

confidence: 74%

“…Most studies of this region have been performed in Caucasians [%17]. Reports from Japanese oriental populations on associations between 5' variable number of tandem repeats (VNTR) polymorphisms in the INS region and IDDM have not been able to show significant association [18][19][20][21][22].…”

mentioning

confidence: 99%

IDDM susceptibility associated with polymorphisms in the insulin gene region A study of blacks, Caucasians and orientals

Undlien¹,

Hamaguchi

Kimura

et al. 1994

Diabetologia

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“…To detect sequence variation caused by the repeat element/ (ACAGGGGTCC CGGGG), we electrophoresed specific PCR products after Sma I digestion on a MetaPhor agarose gel. Since class II and HI alleles are not amplified by the above protocol, Southern blot analysis was also performed as described previously (19). Tyrosine hydroxylase gene microsatellite and IGF2Apa I polymorphism.…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 95% of Japanese are homozygous for class I alleles (17), which makes it difficult to assess the role of the allele in IDDM development in Japanese. However, it has been revealed that class I alleles are variable in length (18,19), and recent studies in Caucasians have provided some evidence that variation in class I (13) or class IE (12,13) alleles influences disease susceptibility. Therefore, in the present study, we have analyzed polymorphisms in the insulin gene and the surrounding region and in particular have evaluated the role of class I variability of INS VNTR in Japanese IDDM patients.…”

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confidence: 99%

Evidence for Association Between the Class I Subset of the Insulin Gene Minisatellite (IDDM2 Locus) and IDDM in the Japanese Population

et al. 1997

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Although the shortest (class I) minisatellite (i.e., variable number of tandem repeats [VNTR]) alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, the majority of Japanese are homozygous for class I alleles. Here, we determined the exact length, in number of repeat units (RUs), of class I alleles in Japanese subjects. The distribution of class I alleles in Japanese was trimodal, with peaks located at 32/33, 41, and 44 RUs. The shortest component (i.e., 1S [25-38 RUs]) alleles were significantly increased in the IDDM group compared with the control group (54 vs. 46%; P = 0.040). The 1S/1S genotype was significantly increased in the IDDM patients (34 vs. 20%; P = 0.005; relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with 1S/1M or 1S/1L heterozygous parents confirmed the association of 1S alleles; 17 alleles of 1S and 6 alleles of 1M (39-41 RUs) or 1L (42-44 RUs) were transmitted to affected offspring (P = 0.022). In addition, we found tight linkage of 1S with allele 9 of the tyrosine hydroxylase gene microsatellite and allele (-) of the IGF-II gene Apa I polymorphism, but neither 9 nor (-) alleles were significantly associated with IDDM. The present study suggests that a class I subset may have a role in IDDM susceptibility in Japan. It was revealed that the difference between 1S alleles and 1M or 1L alleles is almost consistently characterized by a sequence variation generated by deletion of two copies of an ACAGGGGTCC CGGGG repeat element, implying that sequence variation of class I alleles may influence disease susceptibility.

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“…Известно, что частота ал-леля А в китайской и японской популяциях состав-ляет 93 и 97% соответственно [13,17,21], и подавля-ющее большинство представителей азиатских попу-ляций гомозиготны по 5`VNTR INS I класса. Столь высокая частота диабетогенного признака наряду с чрезвычайно низкой заболеваемостью СД1 в азиат-ских популяциях (на порядок ниже, чем у европеои-дов) [22] осложняет поиск ассоциаций [23,24] и мо-жет свидетельствовать о минорной роли признака в патогенезе заболевания.…”

Section: результаты и обсуждениеunclassified

Dimorphism -23HphI in the INS gene (rs689): the association with type 1 diabetes mellitus in the populations of the Russian Federation, the inter-population comparison of the frequencies

Ivanova

Stepanova

Smirnova

et al. 2014

Probl Endokrinol (Mosk)

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Objective. The objective of the present study was to elucidate the association between dimorfism -23HphI in the INS gene (rs689) and type 1 diabetes mellitus in several populations of the Russian Federation and to compare the frequency of alleles of this dimorphism in different populations. Material and methods. The case-control association was investigated in five populations of the Russian Federation, viz. Russian, Bashkir, Udmurtian, Yakutian, and Buryat ones. The DNA samples from 528 patients presenting with type 1 diabetes mellitus and 439 control subjects were available for the investigation, Polymorphism typing was performed using the RFLP-PCR technique. The degree of association of the trait of interest with the disease was estimated based on the odd ratio (OR) values. The calculations were made with the use of Statistica software package, version 6, www.statsoff.com and Microsoft Office Excel-2003. Results. The statistically significant association of type 1 diabetes mellitus with T allele and AA rs689 genotype was documented for the Russian, Bashkir, Udmurtian, and Yakutian populations. The protective marker in these populations were T allele and T+ genotype. A similar association was not found for the Buryat population characterized by the lowest diabetes morbidity rate. This population was significantly different from the remaining ones in the high frequency of A allele (87% vs 69-75%; p є [0.0002-0.004]) and AA genotype (77% vs 45-60%; p є [0.00006-0.01]). Conclusion. This study has demonstrated the inter-population differences in the frequency of rs689 alleles and the population-specific differences in the association of rs689 alleles with type 1 diabetes mellitus. It is concluded that the consideration of population-related peculiarities of clinical and genetic associations is an indispensable precondition for the further development of personalized medicine.

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Lack of association of the insulin gene region with Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects

Cited by 13 publications

References 22 publications

IDDM susceptibility associated with polymorphisms in the insulin gene region A study of blacks, Caucasians and orientals

IDDM susceptibility associated with polymorphisms in the insulin gene region A study of blacks, Caucasians and orientals

Evidence for Association Between the Class I Subset of the Insulin Gene Minisatellite (IDDM2 Locus) and IDDM in the Japanese Population

Dimorphism -23HphI in the INS gene (rs689): the association with type 1 diabetes mellitus in the populations of the Russian Federation, the inter-population comparison of the frequencies

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