Family studies of non-insulin-dependent diabetes mellitus in South Indians

Abstract

Summary Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70 %) diabetic and 11 of 128 (9 %) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and nontransmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in nondiabetic family members (diathesis) was included, if) support for segregation of a dialletic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d---0.8) and a disease-predisposing allele frequency of 14 %. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes. [Diabetologia (1994[Diabetologia ( ) 37: 1221[Diabetologia ( -1230

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes

“…Two previously described neutral polymorphisms in exon 3 (codon 99T®C) and on exon 5 (codon 200C®T) [15] were found in our sample group. At codon 99 of the UCP3 gene 14 of 15 subjects sequenced had the T allele; the one remaining subject had the variant C allele and was homozygotic for the D allele at exon 8 of the UCP2 gene.…”

“…The effect of genetic variants might therefore be more pronounced in an ethnic group as yet not fully exposed to environmental factors that promote obesity compared with one in which the majority of the recent rise in the prevalence of obesity can be explained by modern lifestyle. Secondly, we had access to well characterised study groups including population and family based samples [14,15]. On finding an association between the exon 8 UCP2 variant and BMI, we then proceeded to study a British Caucasoid group for an association with overt obesity.…”

Haplotype Combinations of Calpain 10 Gene Polymorphisms Associate With Increased Risk of Impaired Glucose Tolerance and Type 2 Diabetes in South Indians

“…A total of 95 South Indian families were recruited from a diabetic clinic in Chennai, India. Ascertainment was via an offspring with type 2 diabetes, as defined by recent World Health Organization (WHO) criteria and as previously described (5,6). Of the probands, 63.5% were male, with a mean age of onset for type 2 diabetes of 34 years (range 29 -38), a mean BMI of 26.5 Ϯ 4.5 kg/m 2 , and a mean waist-to-hip ratio (WHR) of 0.94 Ϯ 0.05.…”

Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin

“…South Indian parent-offspring trios (n = 85, all Dravidian) were ascertained in Chennai, India through Type II (non-insulin-dependent) diabetic offspring, as described previously [30,32]. Clinical details of probands are provided in Table 1.…”